显示样式:     当前分类: 医药    当前期刊: Journal of Nuclear Medicine    加入关注    导出
我的关注
我的收藏
您暂时未登录!
登录
  • PET/MRI for Oncologic Brain Imaging: A Comparison of Standard MR-Based Attenuation Corrections with a Model-Based Approach for the Siemens mMR PET/MR System
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    Ivo Rausch; Lucas Rischka; Claes N. Ladefoged; Julia Furtner; Matthias Fenchel; Andreas Hahn; Rupert Lanzenberger; Marius E. Mayerhoefer; Tatjana Traub-Weidinger; Thomas Beyer

    The aim of this study was to compare attenuation-correction (AC) approaches for PET/MRI in clinical neurooncology. Methods: Forty-nine PET/MRI brain scans were included: brain tumor studies using 18F-fluoro-ethyl-tyrosine (18F-FET) (n = 31) and 68Ga-DOTANOC (n = 7) and studies of healthy subjects using 18F-FDG (n = 11). For each subject, MR-based AC maps (MR-AC) were acquired using the standard DIXON- and ultrashort echo time (UTE)–based approaches. A third MR-AC was calculated using a model-based, postprocessing approach to account for bone attenuation values (BD, noncommercial prototype software by Siemens Healthcare). As a reference, AC maps were derived from patient-specific CT images (CTref). PET data were reconstructed using standard settings after AC with all 4 AC methods. We report changes in diagnosis for all brain tumor patients and the following relative differences values (RDs [%]), with regards to AC-CTref: for 18F-FET (A)—SUVs as well as volumes of interest (VOIs) defined by a 70% threshold of all segmented lesions and lesion-to-background ratios; for 68Ga-DOTANOC (B)—SUVs as well as VOIs defined by a 50% threshold for all lesions and the pituitary gland; and for 18F-FDG (C)—RD of SUVs of the whole brain and 10 anatomic regions segmented on MR images. Results: For brain tumor imaging (A and B), the standard PET-based diagnosis was not affected by any of the 3 MR-AC methods. For A, the average RDs of SUVmean were −10%, −4%, and −3% and of the VOIs 1%, 2%, and 7% for DIXON, UTE, and BD, respectively. Lesion-to-background ratios for all MR-AC methods were similar to that of CTref. For B, average RDs of SUVmean were −11%, −11%, and −3% and of the VOIs 1%, −4%, and −3%, respectively. In the case of 18F-FDG PET/MRI (C), RDs for the whole brain were −11%, −8%, and −5% for DIXON, UTE, and BD, respectively. Conclusion: The diagnostic reading of PET/MR patients with brain tumors did not change with the chosen AC method. Quantitative accuracy of SUVs was clinically acceptable for UTE- and BD-AC for group A, whereas for group B BD was in accordance with CTref. Nevertheless, for the quantification of individual lesions large deviations to CTref can be observed independent of the MR-AC method used.

    更新日期:2017-09-05
  • Studies of a Next-Generation Silicon-Photomultiplier–Based Time-of-Flight PET/CT System
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    David F.C. Hsu; Ezgi Ilan; William T. Peterson; Jorge Uribe; Mark Lubberink; Craig S. Levin

    This article presents system performance studies for the Discovery MI PET/CT system, a new time-of-flight system based on silicon photomultipliers. System performance and clinical imaging were compared between this next-generation system and other commercially available PET/CT and PET/MR systems, as well as between different reconstruction algorithms. Methods: Spatial resolution, sensitivity, noise-equivalent counting rate, scatter fraction, counting rate accuracy, and image quality were characterized with the National Electrical Manufacturers Association NU-2 2012 standards. Energy resolution and coincidence time resolution were measured. Tests were conducted independently on two Discovery MI scanners installed at Stanford University and Uppsala University, and the results were averaged. Back-to-back patient scans were also performed between the Discovery MI, Discovery 690 PET/CT, and SIGNA PET/MR systems. Clinical images were reconstructed using both ordered-subset expectation maximization and Q.Clear (block-sequential regularized expectation maximization with point-spread function modeling) and were examined qualitatively. Results: The averaged full widths at half maximum (FWHMs) of the radial/tangential/axial spatial resolution reconstructed with filtered backprojection at 1, 10, and 20 cm from the system center were, respectively, 4.10/4.19/4.48 mm, 5.47/4.49/6.01 mm, and 7.53/4.90/6.10 mm. The averaged sensitivity was 13.7 cps/kBq at the center of the field of view. The averaged peak noise-equivalent counting rate was 193.4 kcps at 21.9 kBq/mL, with a scatter fraction of 40.6%. The averaged contrast recovery coefficients for the image-quality phantom were 53.7, 64.0, 73.1, 82.7, 86.8, and 90.7 for the 10-, 13-, 17-, 22-, 28-, and 37-mm-diameter spheres, respectively. The average photopeak energy resolution was 9.40% FWHM, and the average coincidence time resolution was 375.4 ps FWHM. Clinical image comparisons between the PET/CT systems demonstrated the high quality of the Discovery MI. Comparisons between the Discovery MI and SIGNA showed a similar spatial resolution and overall imaging performance. Lastly, the results indicated significantly enhanced image quality and contrast-to-noise performance for Q.Clear, compared with ordered-subset expectation maximization. Conclusion: Excellent performance was achieved with the Discovery MI, including 375 ps FWHM coincidence time resolution and sensitivity of 14 cps/kBq. Comparisons between reconstruction algorithms and other multimodal silicon photomultiplier and non–silicon photomultiplier PET detector system designs indicated that performance can be substantially enhanced with this next-generation system.

    更新日期:2017-09-05
  • 18F-FDG PET/CT Optimizes Treatment in Staphylococcus Aureus Bacteremia and Is Associated with Reduced Mortality
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    Marvin A.H. Berrevoets; Ilse J.E. Kouijzer; Erik H.J.G. Aarntzen; Marcel J.R. Janssen; Lioe-Fee De Geus-Oei; Heiman F.L. Wertheim; Bart-Jan Kullberg; Jaap Ten Oever; Wim J.G. Oyen; Chantal P. Bleeker-Rovers

    Metastatic infection is an important complication of Staphylococcus aureus bacteremia (SAB). Early diagnosis of metastatic infection is crucial, because specific treatment is required. However, metastatic infection can be asymptomatic and difficult to detect. In this study, we investigated the role of 18F-FDG PET/CT in patients with SAB for detection of metastatic infection and its consequences for treatment and outcome. Methods: All patients with SAB at Radboud University Medical Center were included between January 2013 and April 2016. Clinical data and results of 18F-FDG PET/CT and other imaging techniques, including echocardiography, were collected. Primary outcomes were newly diagnosed metastatic infection by 18F-FDG PET/CT, subsequent treatment modifications, and patient outcome. Results: A total of 184 patients were included, and 18F-FDG PET/CT was performed in 105 patients, of whom 99 had a high-risk bacteremia. 18F-FDG PET/CT detected metastatic infectious foci in 73.7% of these high-risk patients. In 71.2% of patients with metastatic infection, no signs and symptoms suggesting metastatic complications were present before 18F-FDG PET/CT was performed. 18F-FDG PET/CT led to a total of 104 treatment modifications in 74 patients. Three-month mortality was higher in high-risk bacteremia patients without 18F-FDG PET/CT performed than in those in whom 18F-FDG PET/CT was performed (32.7% vs. 12.4%, P = 0.003). In multivariate analysis, 18F-FDG PET/CT was the only factor independently associated with reduced mortality (P = 0.005; odds ratio, 0.204; 95% confidence interval, 0.066–0.624). A higher comorbidity score was independently associated with increased mortality (P = 0.003; odds ratio, 1.254; 95% confidence interval, 1.078–1.457). Conclusion: 18F-FDG PET/CT is a valuable technique for early detection of metastatic infectious foci, often leading to treatment modification. Performing 18F-FDG PET/CT is associated with significantly reduced 3-mo mortality.

    更新日期:2017-09-05
  • Biodistribution and Radiation Dosimetry for the Tau Tracer 18F-THK-5351 in Healthy Human Subjects
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    Ing-Tsung Hsiao; Kun-Ju Lin; Kuo-Lun Huang; Chin-Chang Huang; Han-Shiuan Chen; Shiaw-Pyng Wey; Tzu-Chen Yen; Nobuyuki Okamura; Jung-Lung Hsu

    18F-THK-5351 is a novel radiotracer that demonstrates high binding selectivity and affinity for tau pathology and exhibits better pharmacokinetics in the living brain than previous THK tau probes. The aim of the present study was to estimate the radiation dose of 18F-THK-5351 in humans and to compare the clinical radiation dosimetry results to estimations published previously with preclinical data. Methods: Serial whole-body PET/CT imaging was performed for 240 min on 12 healthy volunteers after injecting 18F-THK-5351 (mean administered activity, 377.8 ± 14.0 MBq; range, 340–397 MBq). The bladder and gallbladder were delineated on PET images, and the other organs were delineated on CT images. Voided urine activity was recorded. The decay-corrected and normalized 18F-THK-5351 activity of 15 source-organ regions as a function of time was entered into the OLINDA/EXM software to calculate the effective dose for each subject following the medical internal radiation dosimetry schema. Results: Overall, the 18F-THK-5351 injection was well tolerated. The highest mean initial uptake at 10 min after injection was in the liver (11.4% ± 2.0%), lung (5.7% ± 2.1%), intestine (3.4% ± 0.8%), and kidney (1.4% ± 0.3%). The highest mean absorbed dose of radiation was in the gallbladder wall (242.2 ± 105.2 μGy/MBq), upper large intestine (90.0 ± 15.8 μGy/MBq), small intestine (79.5 ± 13.8 μGy/MBq), and liver (55.8 ± 6.1 μGy/MBq). The resultant whole-body effective dose was 22.7 ± 1.3 μSv/MBq. Conclusion: Our results suggest that a routine injection of 370 MBq of 18F-THK-5351 would lead to an estimated effective dose of 8.4 mSv; hence, 18F-THK-5351 has a radiation burden similar to that of other commonly used clinical tracers. Our findings in humans were compatible with recently published preclinical dosimetry data extrapolated from mice.

    更新日期:2017-09-05
  • Alteration of Monoamine Receptor Activity and Glucose Metabolism in Pediatric Patients with Anticonvulsant-Induced Cognitive Impairment
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    Yuankai Zhu; Jianhua Feng; Jianfeng Ji; Haifeng Hou; Lin Chen; Shuang Wu; Qing Liu; Qiong Yao; Peizhen Du; Kai Zhang; Qing Chen; Zexin Chen; Hong Zhang; Mei Tian

    A landmark study from the Institute of Medicine reported that the assessment of cognitive difficulties in children with epilepsy is timely and imperative. Anticonvulsant-induced cognitive impairment could influence the quality of life more than seizure itself in patients. Although the monoaminergic system is involved in the regulation of cognitive process, its role in anticonvulsant-induced cognitive impairment remains unclear. Methods: To explore in vivo monoamine receptor binding activity in patients with anticonvulsant-induced cognitive impairment, each patient underwent PET imaging with both monoamine receptor binding agent 11C-N-methylspiperone and glucose metabolic agent 18F-FDG. Tests of intelligence quotient (IQ), including verbal IQ (VIQ), performance IQ (PIQ), and full-scale IQ (FSIQ), were performed in each patient. Results: Compared with the patients with monotherapy, patients with polytherapy had significantly lower VIQ, PIQ, and FSIQ (P < 0.01 in each comparison), as well as significantly lower monoamine receptor activities detected in the caudate nucleus, prefrontal cortex, dorsal anterior cingulate cortex, and amygdale (P < 0.05 in each comparison). However, regarding the glucose metabolism, there was no significant difference found in patients with monotherapy or polytherapy (P > 0.05). Conclusion: Monoamine receptor PET imaging could be a promising in vivo imaging biomarker for mapping anticonvulsant-induced cognitive impairment.

    更新日期:2017-09-05
  • Validation of the Semiquantitative Static SUVR Method for 18F-AV45 PET by Pharmacokinetic Modeling with an Arterial Input Function
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    Julie Ottoy; Jeroen Verhaeghe; Ellis Niemantsverdriet; Leonie Wyffels; Charisse Somers; Ellen De Roeck; Hanne Struyfs; Femke Soetewey; Steven Deleye; Tobi Van den Bossche; Sara Van Mossevelde; Sarah Ceyssens; Jan Versijpt; Sigrid Stroobants; Sebastiaan Engelborghs; Steven Staelens

    Increased brain uptake of 18F-AV45 visualized by PET is a key biomarker for Alzheimer disease (AD). The SUV ratio (SUVR) is widely used for quantification, but is subject to variability based on choice of reference region and changes in cerebral blood flow. Here we validate the SUVR method against the gold standard volume of distribution (VT) to assess cross-sectional differences in plaque load. Methods: Dynamic 60-min 18F-AV45 (291 ± 67 MBq) and 1-min 15O-H2O (370 MBq) scans were obtained in 35 age-matched elderly subjects, including 10 probable AD, 15 amnestic mild cognitive impairment (aMCI), and 10 cognitively healthy controls (HCs). 18F-AV45 VT was determined from 2-tissue-compartment modeling using a metabolite-corrected plasma input function. Static SUVR was calculated at 50–60 min after injection, using either cerebellar gray matter (SUVRCB) or whole subcortical white matter (SUVRWM) as the reference. Additionally, whole cerebellum, pons, centrum semiovale, and a composite region were examined as alternative references. Blood flow was quantified by 15O-H2O SUV. Data are presented as mean ± SEM. Results: There was rapid metabolization of 18F-AV45, with only 35% of unchanged parent remaining at 10 min. Compared with VT, differences in cortical Aβ load between aMCI and AD were overestimated by SUVRWM (+4% ± 2%) and underestimated by SUVRCB (−10% ± 2%). VT correlated better with SUVRWM (Pearson r: from 0.63 for posterior cingulate to 0.89 for precuneus, P < 0.0001) than with SUVRCB (Pearson r: from 0.51 for temporal lobe [P = 0.002] to 0.82 for precuneus [P < 0.0001]) in all tested regions. Correlation results for the alternative references were in between those for CB and WM. 15O-H2O data showed that blood flow was decreased in AD compared with aMCI in cortical regions (−5% ± 1%) and in the reference regions (CB, −9% ± 8%; WM, −8% ± 8%). Conclusion: Increased brain uptake of 18F-AV45 assessed by the simplified static SUVR protocol does not truly reflect Aβ load. However, SUVRWM is better correlated with VT and more closely reflects VT differences between aMCI and AD than SUVRCB.

    更新日期:2017-09-05
  • 11C-PBR28 and 18F-PBR111 Detect White Matter Inflammatory Heterogeneity in Multiple Sclerosis
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    Gourab Datta; Alessandro Colasanti; Nicola Kalk; David Owen; Gregory Scott; Eugenii A. Rabiner; Roger N. Gunn; Anne Lingford-Hughes; Omar Malik; Olga Ciccarelli; Richard Nicholas; Lei Nei; Marco Battaglini; Nicola D. Stefano; Paul M. Matthews

    The objective of this study was to assess microglial activation in lesions and in normal-appearing white matter (NAWM) of multiple sclerosis (MS) patients using PET. Methods: Thirty-four MS patients (7 with secondary progressive MS [SPMS], 27 with relapsing remitting MS [RRMS]) and 30 healthy volunteers, genetically stratified for translocator protein (TSPO) binding status, underwent PET scanning with TSPO radioligands (11C-PBR28 or 18F-PBR111). Regional TSPO availability was measured as a distribution volume ratio (DVR) relative to the caudate (a pseudoreference region). White matter lesions (WMLs) were classified as “active” (DVR highest in the lesion), “peripherally active” (perilesional DVR highest), “inactive” (DVR highest in surrounding NAWM), or “undifferentiated” (similar DVR across lesion, perilesional and NAWM volumes). Results: The mean DVR in NAWM of patients was greater than that of the healthy volunteer white matter for both radioligands. Uptake for individual WML in patients was heterogeneous, but the median WML DVR and NAWM DVR for individual patients were strongly correlated (ρ = 0.94, P = 4 × 10−11). A higher proportion of lesions were inactive in patients with SPMS (35%) than RRMS (23%), but active lesions were found in all patients, including those on highly efficacious treatments. Conclusion: TSPO radioligand uptake was increased in the brains of MS patients relative to healthy controls with 2 TSPO radiotracers. WML showed heterogeneous patterns of uptake. Active lesions were found in patients with both RRMS and SPMS. Their independent prognostic significance needs further investigation.

    更新日期:2017-09-05
  • Cerebrospinal Fluid Clearance in Alzheimer Disease Measured with Dynamic PET
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    Mony J. de Leon; Yi Li; Nobuyuki Okamura; Wai H. Tsui; Les A. Saint-Louis; Lidia Glodzik; Ricardo S. Osorio; Juan Fortea; Tracy Butler; Elizabeth Pirraglia; Silvia Fossati; Hee-Jin Kim; Roxana O. Carare; Maiken Nedergaard; Helene Benveniste; Henry Rusinek

    Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer disease (AD) comes primarily from rodent models. However, unlike rodents, in which predominant extracranial CSF egress is via olfactory nerves traversing the cribriform plate, human CSF clearance pathways are not well characterized. Dynamic PET with 18F‐THK5117, a tracer for tau pathology, was used to estimate the ventricular CSF time–activity as a biomarker for CSF clearance. We tested 3 hypotheses: extracranial CSF is detected at the superior turbinates; CSF clearance is reduced in AD; and CSF clearance is inversely associated with amyloid deposition. Methods: Fifteen subjects, 8 with AD and 7 normal control volunteers, were examined with 18F‐THK5117. Ten subjects additionally underwent 11C-Pittsburgh compound B (11C-PiB) PET scanning, and 8 were 11C-PiB–positive. Ventricular time–activity curves of 18F‐THK5117 were used to identify highly correlated time–activity curves from extracranial voxels. Results: For all subjects, the greatest density of CSF-positive extracranial voxels was in the nasal turbinates. Tracer concentration analyses validated the superior nasal turbinate CSF signal intensity. AD patients showed ventricular tracer clearance reduced by 23% and 66% fewer superior turbinate CSF egress sites. Ventricular CSF clearance was inversely associated with amyloid deposition. Conclusion: The human nasal turbinate is part of the CSF clearance system. Lateral ventricle and superior nasal turbinate CSF clearance abnormalities are found in AD. Ventricular CSF clearance reductions are associated with increased brain amyloid depositions. These data suggest that PET-measured CSF clearance is a biomarker of potential interest in AD and other neurodegenerative diseases.

    更新日期:2017-09-05
  • Initial Evaluation of an Adenosine A2A Receptor Ligand, 11C-Preladenant, in Healthy Human Subjects
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    Muneyuki Sakata; Kenji Ishibashi; Masamichi Imai; Kei Wagatsuma; Kenji Ishii; Xiaoyun Zhou; Erik F.J. de Vries; Philip H. Elsinga; Kiichi Ishiwata; Jun Toyohara

    11C-preladenant is a selective antagonist for mapping of cerebral adenosine A2A receptors (A2ARs) by PET. This is a first-in-human study to examine the safety, radiation dosimetry, and brain imaging of 11C-preladenant in healthy human subjects. Methods: Dynamic 11C-preladenant PET scans (90 min) were obtained in 5 healthy male subjects. During the scan, arterial blood was sampled at various time intervals, and the fraction of the parent compound in plasma was determined. For anatomic coregistration, T1-weighted MRI was performed. The total distribution volume (VT) was estimated using 1- and 2-tissue-compartment models (1T and 2T, respectively). The distribution volume ratio (DVR) was calculated from VT of target and reference region and obtained with a noninvasive Logan graphical reference tissue method (t* = 30 min). The applicability of a shortened protocol as an alternative to the 90-min PET scan was investigated. Tracer biodistribution and dosimetry were determined in 3 healthy male subjects, using serial whole-body PET scans acquired over 2 h after 11C-preladenant injection. Results: There were no serious adverse events in any of the subjects throughout the study period. 11C-preladenat readily entered the brain, with a peak uptake in the putamen and head of the caudate nucleus 30−40 min after tracer injection. Other brain regions showed rapid clearance of radioactivity. The regional distribution of 11C-preladenant was consistent with known A2AR densities in the brain. At pseudoequilibrium (reached at 40 min after injection), stable target–to–cerebellar cortex ratios of around 3.8−10.0 were obtained. The 2T fit better than the 1T in the low-density A2AR regions. In contrast, there were no significant differences between 1T and 2T in the high-A2AR-density regions. DVRs in the putamen and head of the caudate nucleus were around 3.8−10.3 when estimated using a Logan graphical reference tissue method with cerebellum as the reference region. PET scanning at 50 or 70 min can provide the stable DVR estimates within 10% or 5% differences at most, respectively. The radioactivity was mainly excreted through the hepatobiliary system after 11C-preladenant injection. As a result, the absorbed dose (μGy/MBq) was highest in the gallbladder wall (mean ± SD, 17.0 ± 2.5) and liver (11.7 ± 2.1). The estimated effective dose for 11C-preladenant was 3.7 ± 0.4 μSv/MBq. Conclusion: This initial evaluation indicated that 11C-preladenat is suitable for imaging of A2ARs in the brain.

    更新日期:2017-09-05
  • Prognostic Value of Myocardial Perfusion Imaging with a Cadmium-Zinc-Telluride SPECT Camera in Patients Suspected of Having Coronary Artery Disease
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    Elsemiek M. Engbers; Jorik R. Timmer; Mohamed Mouden; Siert Knollema; Pieter L. Jager; Jan Paul Ottervanger

    The prognostic value of myocardial perfusion imaging (MPI) with the cadmium-zinc-telluride (CZT) SPECT camera is not well established. Therefore, the aim of the current study was to evaluate the prognostic value of MPI performed with a CZT SPECT camera in a large cohort of patients suspected of having coronary artery disease. Methods: Consecutive symptomatic stable patients (n = 4,057) without a history of coronary artery disease underwent CZT SPECT MPI. During a median follow-up of 2.4 y (25th–75th percentile, 1.7–3.4), patients were monitored for primary (nonfatal myocardial infarction and cardiac mortality) and secondary outcomes (late revascularization [>90 d after scanning] and primary outcome). Results: Patients with normal perfusion demonstrated low annual event rates (primary outcome, 0.2%; secondary outcome, 0.6%). Annual event rates increased with the extent of abnormality of myocardial perfusion. In patients with small ischemic perfusion defects, annual event rates were 0.7% and 2.8% for the primary and secondary outcome, respectively. In patients with moderate or large ischemic perfusion defects, these event rates were 1.2% and 4.3%, respectively. After multivariate analysis, the risk for events was significantly associated with the extent of ischemia (hazard ratio for small ischemic defects: 2.2, 95% confidence interval [CI], 0.9–5.9 and 4.6, 95% CI, 2.8–7.6, for primary and secondary outcomes, respectively; hazard ratio for moderate or large ischemic defects: 4.0, 95% CI, 1.5–10.5 and 12.1, 95% CI, 7.2–20.2, for primary and secondary outcomes, respectively). Conclusion: Our findings show that MPI acquired with a CZT SPECT camera provides excellent prognostic information, with low event rates in patients with normal myocardial perfusion. In patients with abnormal SPECT MPI, the extent of abnormality is independently associated with an increased risk of events.

    更新日期:2017-09-05
  • 68Ga-DOTATOC Imaging of Neuroendocrine Tumors: A Systematic Review and Metaanalysis
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    Michael M. Graham; Xiaomei Gu; Timothy Ginader; Patrick Breheny; John J. Sunderland

    68Ga-DOTATOC, a somatostatin receptor–targeted ligand, has been used clinically in Europe over the past decade for imaging neuroendocrine tumors (NETs). It appears to be quite sensitive and effective for clinical management decision making. This metaanalysis summarizes the efficacy of 68Ga-DOTATOC for several distinct indications and is intended to support approval of this agent by the U.S. Food and Drug Administration. Methods: The major electronic medical databases were searched for relevant papers over the period from January 2001 to November 2015. Papers were selected for review in 3 categories: clinical trials that reported sensitivity and specificity, comparison studies with 111In-octreotide, and change of management studies. All the eligible papers underwent Quality Assessment of Diagnostic Accuracy Studies (QUADAS) assessment, which was useful in the final selection of papers for review. Results: The initial search yielded 468 papers. After detailed evaluation, 17 papers were finally selected. Five types of studies emerged: workup of patients with symptoms and biomarker findings suggestive of NET, but with negative conventional imaging (3 papers, yield was only 13%); sensitivity (12 papers; sensitivity, 92%) and specificity (7 papers; specificity, 82%); identification of site of unknown primary in patients with metastatic NET (4 papers, yield was 44%); impact on subsequent NET patient management (4 papers, change in management in 51%); and comparison with 111In-octreotide (2 papers, sensitivity of DOTATOC on a per-lesion basis was 100%, for 111In-octreotide it was 78.2%; specificity was not available). Safety was not explicitly addressed in any study, but there were no reports of adverse events. Conclusion: 68Ga-DOTATOC is useful for evaluating the presence and extent in disease for staging and restaging and for assisting in treatment decision making for patients with NET. It is also effective in locating the site of an unknown primary in NET patients who present with metastatic NET, but no known primary tumor. It also appears to be more accurate than 111In-octreotide. Although 68Ga-DOTATOC would seem to be useful in evaluating patients with suggestive symptoms and biomarker findings, it does not perform well in this setting and has low yield. Overall, it appears to be an excellent imaging agent to assess patients with known NET and frequently leads to a change in management.

    更新日期:2017-09-05
  • Dual-Target Binding Ligands with Modulated Pharmacokinetics for Endoradiotherapy of Prostate Cancer
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    James M. Kelly; Alejandro Amor-Coarasa; Anastasia Nikolopoulou; Till Wüstemann; Peter Barelli; Dohyun Kim; Clarence Williams, Jr; Xiwei Zheng; Cong Bi; Bao Hu; J. David Warren; David S. Hage; Stephen G. DiMagno; John W. Babich

    Prostate-specific membrane antigen (PSMA)–targeted radiotherapy of prostate cancer (PCa) has emerged recently as a promising approach to the treatment of disseminated disease. A small number of ligands have been evaluated in patients, and although early tumor response is encouraging, relapse rate is high and these compounds localize to the parotid, salivary, and lacrimal glands as well as to the kidney, leading to dose-limiting toxicities and adverse events affecting quality of life. We envision that dual-target binding ligands displaying high affinity for PSMA and appropriate affinity for human serum albumin (HSA) may demonstrate a higher therapeutic index and be suitable for treatment of PCa by targeted α-therapy. Methods: Six novel urea-based ligands with varying affinities for PSMA and HSA were synthesized, labeled with 131I, and evaluated by in vitro binding and uptake assays in LNCaP cells. Four compounds were advanced for further evaluation in a preclinical model of PCa. The compounds were compared with MIP-1095, a PSMA ligand currently in clinical evaluation. Results: The compounds demonstrated affinity for PSMA on the order of 4–40 nM and affinity for HSA in the range of 1–53 μM. Compounds with relatively high affinity for HSA (≤2 μM) showed high and sustained blood-pool activity and reduced uptake in the kidneys. 131I-RPS-027, with a 50% inhibitory concentration (PSMA) of 15 nM and a dissociation constant (HSA) of 11.2 μM, cleared from the blood over the course of 48 h and showed good tumor uptake (10 percentage injected dose per gram) and retention and a greater than 5-fold decrease in kidney uptake relative to MIP-1095. The tumor-to-kidney ratio of 131I-RPS-027 was greater than 3:1 at 24 h after injection, increasing to 7:1 by 72 h. Conclusion: RPS-027 shows dual targeting to PSMA and albumin, resulting in a high tumor uptake, highly favorable tissue distribution, and promising therapeutic profile in a preclinical model of prostate cancer. In comparison to existing ligands proposed for targeted therapy of prostate cancer, RPS-027 has tumor-to-tissue ratios that predict a significant reduction in side effects during therapy. Using iodine/radioiodine as a surrogate for the radiohalogen 211At, we therefore propose dual-target binding ligands such as RPS-027 as next-generation radiopharmaceuticals for targeted α-therapy using 211At.

    更新日期:2017-09-05
  • Biodistribution, Pharmacokinetics, and Dosimetry of 177Lu-, 90Y-, and 111In-Labeled Somatostatin Receptor Antagonist OPS201 in Comparison to the Agonist 177Lu-DOTATATE: The Mass Effect
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    Guillaume P. Nicolas; Rosalba Mansi; Lisa McDougall; Jens Kaufmann; Hakim Bouterfa; Damian Wild; Melpomeni Fani

    Radiolabeled somatostatin receptor (SSTR) antagonists have shown in vivo higher uptake in SSTR-expressing tumors than agonists. In this preclinical study, the SSTR2 antagonist OPS201 (DOTA-JR11; DOTA-[Cpa-c(DCys-Aph(Hor)-DAph(Cbm)-Lys-Thr-Cys)-DTyr-NH2]) labeled with 177Lu, 90Y, and 111In was compared with the SSTR2 agonist 177Lu-DOTATATE. Methods: Biodistribution, pharmacokinetics, SPECT/CT, and dosimetry studies were performed to assess the bioequivalence of all radiotracers. Use of escalated peptide mass and nephroprotective agents were systematically investigated. Results: The tumor residence time was 15.6 h (13.4–17.7) for 177Lu-OPS201 (10 pmol) and 6.4 h (5.4–7.3) for 177Lu-DOTATATE, resulting in a 2.5-times-higher tumor dose for the antagonist than for the agonist (0.854 vs. 0.333 mGy/MBq for a 4-cm tumor). The overall tumor–to–kidney dose ratio was approximately 24% and 32% higher for 177Lu-OPS201 than for 90Y-OPS201 and 177Lu-DOTATATE, respectively. 111In-OPS201 had a biodistribution significantly different from 90Y-OPS201 and is therefore not a surrogate for 90Y-OPS201 dosimetry studies. Importantly, and in contrast to 177Lu-DOTATATE, injection of 10, 200, and 2,000 pmol of 177Lu-OPS201 did not cause any relevant tumor saturation, with tumor uptake 4 h after injection: 23.9, 24.9, and 18.8 percentage of injected activity per gram of tissue (%IA/g), respectively, for the antagonist (P > 0.05), as compared with 17.8, 12.0, and 9.9 %IA/g for the agonist (P < 0.05). Increasing the peptide mass of 177Lu-OPS201 from 10 to 200 pmol drastically decreased the effective dose from 0.0908 to 0.0184 mSv/MBq and decreased the uptake in the liver, bone marrow, and all SSTR2-expressing organs; thus, the therapeutic index improved considerably. Lysine and succinylated gelatine, alone or in combination, significantly reduced the renal dose of 177Lu-OPS201 compared with the control group, by 45%, 25%, and 40%, respectively (P < 0.05). The reduction was similar for 10 and 200 pmol, whereas lysine performed better than succinylated gelatine. Conclusion: 177Lu-OPS201 exhibits higher tumor uptake, longer tumor residence time, and improved tumor–to–kidney dose ratio compared with 177Lu-DOTATATE and 90Y-OPS201. Importantly, the mass-escalation study indicates that an optimized antagonist mass might further improve the safety window of peptide receptor radionuclide therapy by reducing the liver and bone marrow doses as well as the effective dose. Clinical studies are warranted to confirm the efficacy and advantageous toxicity profile of 177Lu-OPS201.

    更新日期:2017-09-05
  • Quantitation of Cancer Treatment Response by 18F-FDG PET/CT: Multicenter Assessment of Measurement Variability
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    Joo Hyun O; Heather Jacene; Brandon Luber; Hao Wang; Minh-Huy Huynh; Jeffrey P. Leal; Richard L. Wahl

    The aim of this study was to assess the interobserver variability of quantitative 18F-FDG PET/CT parameters used in assessments of treatment response across multiple sites and readers. Methods: Paired pre- and posttreatment 18F-FDG PET/CT images of 30 oncologic patients were distributed to 22 readers across 15 U.S. and international sites. One reader was aware of the full medical history (readreference) of the patients, whereas the 21 other readers were unaware. The readers selected the single hottest tumor from each study, and made SUV measurements from this target lesion and the liver. Descriptive statistics, percentage changes in the measurements, and their agreements were obtained. Results: The intraclass correlation coefficient for the percentage change in SUVmax (%ΔSUVmax) of the hottest tumor was 0.894 (95% confidence interval [CI], 0.813–0.941), and the individual equivalence coefficient was 1.931 (95% CI, 0.568–6.449) when all reads were included (n = 638). When only the measurements that selected the same target tumor as the readreference (n = 486) were included, the intraclass correlation coefficient for the %ΔSUVmax was 0.944 (95% CI, 0.841–0.989), and the individual equivalence coefficient was −0.688 (95% CI, −1.810 to −0.092). The absolute change in SUVmean of liver corrected for lean body mass showed upper and lower limits of agreement (average bias ± 2 SDs) of 0.13 and −0.13 g/mL. Conclusion: The quantitative tumor SUV changes measured across multiple sites and readers show a high correlation. Selection of the same tumor target among readers further increased the degree of correlation.

    更新日期:2017-09-05
  • Prediction of Response to Immune Checkpoint Inhibitor Therapy Using Early-Time-Point 18F-FDG PET/CT Imaging in Patients with Advanced Melanoma
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    Steve Y. Cho; Evan J. Lipson; Hyung-Jun Im; Steven P. Rowe; Esther Mena Gonzalez; Amanda Blackford; Alin Chirindel; Drew M. Pardoll; Suzanne L. Topalian; Richard L. Wahl

    The purpose of this study was to evaluate 18F-FDG PET/CT scanning as an early predictor of response to immune checkpoint inhibitors (ICIs) in patients with advanced melanoma. Methods: Twenty patients with advanced melanoma receiving ICI prospectively underwent 18F-FDG PET/CT at 3 scan intervals: before treatment initiation (SCAN-1), at days 21–28 (SCAN-2), and at 4 mo (SCAN-3). This study was approved by the institutional review board, and informed consent was received from all patients who were enrolled between April 2012 and December 2013. Tumor response at each posttreatment time point was assessed according to RECIST 1.1, immune-related response criteria, PERCIST (PERCIST 1.0), and European Organization for Research and Treatment of Cancer (EORTC) criteria. Performance characteristics of each metric to predict best overall response (BOR) at ≥ 4 mo were assessed. Results: Twenty evaluable patients were treated with ipilimumab (n = 16), BMS-936559 (n = 3), or nivolumab (n = 1). BOR at ≥ 4 mo included complete response (n = 2), partial response (n = 2), stable disease (n = 1), and progressive disease (n = 15). Response evaluations at SCAN-2 using RECIST 1.1, immune-related response criteria, PERCIST, and EORTC criteria demonstrated accuracies of 75%, 70%, 70%, and 65%, respectively, to predict BOR at ≥ 4 mo. Interestingly, the optimal PERCIST and EORTC threshold values at SCAN-2 to predict BOR were >15.5% and >14.7%, respectively. By combining anatomic and functional imaging data collected at SCAN-2, we developed criteria to predict eventual response to ICI with 100% sensitivity, 93% specificity, and 95% accuracy. Conclusion: Combining functional and anatomic imaging parameters from 18F-FDG PET/CT scans performed early in ICI appears predictive for eventual response in patients with advanced melanoma. These findings require validation in larger cohorts.

    更新日期:2017-09-05
  • Role of 18F-FDG PET/CT in Posttreatment Evaluation of Anal Carcinoma
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    Clémence Houard; Jean-Baptiste Pinaquy; Charles Mesguich; Bénédicte Henriques de Figueiredo; Anne-Laure Cazeau; Jean-Baptiste Allard; Hortense Laharie; Laurence Bordenave; Philippe Fernandez; Véronique Vendrely

    The aim of this study was to evaluate the relevance of PET/CT and 18F-FDG as a strategy for response evaluation after chemoradiotherapy for anal cancer. For this, the performance of posttreatment 18F-FDG PET/CT, the impact on patient care, and the predictive value of metabolic response were assessed. Methods: This was a retrospective and multicenter analysis of 87 patients treated by chemoradiotherapy for anal squamous cell carcinoma between October 2007 and October 2013. All patients underwent systematic posttreatment 18F-FDG PET/CT and were followed with at least a clinical examination every 4 mo for 2 y and every 6 mo thereafter. Disease progression was confirmed by biopsy for all patients in the case of local recurrence before surgery. Kaplan–Meier and Cox regression models were used to test for associations between metabolic or clinical endpoints and progression-free survival (PFS) or cause-specific survival (CSS). Results: The median follow-up was 25 mo. 18F-FDG PET/CT was performed 1–8 mo (median, 4 mo) after completion of chemoradiotherapy. Overall, 25 patients relapsed and 13 died. The posttherapy 18F-FDG PET/CT did not show any abnormal 18F-FDG uptake (complete metabolic response [CMR]) in 55 patients whereas 32 displayed incomplete response (non-CMR): 15 patients with partial response and 17 with disease progression. The sensitivity of 18F-FDG PET/CT to detect residual tumor tissue was 92% (95% confidence interval [CI], 75%–97%), specificity was 85% (95% CI, 75%–92%), positive predictive value was 72% (95% CI, 61%–90%), and negative predictive value was 96.4% (95% CI, 90%–98.7%). The 2-y PFS was 96% (95% CI, 90–100) for patients with CMR and 28% (95% CI, 14–47) for non-CMR patients (P < 0.0001). The 2-y CSS was 100% for patients with CMR and 59% (95% CI, 42–84) for those without CMR (P < 0.0001). 18F-FDG PET/CT changed patient management in 14 cases (16%), with relevant modifications in 12 (14%). A Cox proportional hazards model of survival outcome indicated that a CMR was the only significant predictor of PFS and CSS (P < 0.0001). Conclusion: 18F-FDG PET/CT shows good accuracy in posttreatment evaluation of anal cancer and has a relevant impact on patient management. Moreover, CMR is associated with good survival outcome. Thus, 18F-FDG PET/CT may play a significant role during posttreatment follow-up of anal cancer.

    更新日期:2017-09-05
  • Phase 2 Study of 99mTc-Trofolastat SPECT/CT to Identify and Localize Prostate Cancer in Intermediate- and High-Risk Patients Undergoing Radical Prostatectomy and Extended Pelvic LN Dissection
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    Karolien E. Goffin; Steven Joniau; Peter Tenke; Kevin Slawin; Eric A. Klein; Nancy Stambler; Thomas Strack; John Babich; Thomas Armor; Vivien Wong

    99mTc-trofolastat (99mTc-MIP-1404), a small-molecule inhibitor of prostate-specific membrane antigen, shows high potential to detect prostate cancer (PCa) noninvasively using SPECT. We therefore wanted to assess the performance of 99mTc-trofolastat SPECT/CT in a phase 2 multicenter, multireader prospective study in patients with intermediate- and high-grade PCa, before radical prostatectomy and extended pelvic lymph node (LN) dissection, with histopathology as the gold standard. Methods: PCa patients (n = 105) with an increased risk of LN involvement (LNI) underwent pelvic 99mTc-trofolastat SPECT/CT before radical prostatectomy with extended pelvic LN dissection. The sensitivity of 99mTc-trofolastat for detection of PCa on a patient and lobe basis, using visual and semiquantitative (tumor-to-background ratio [TBR]) scores, and of LNI was evaluated as well as the correlation of uptake within the gland to Gleason scores (GS) and assessment of the predictive potential of 99mTc-trofolastat uptake for LNI. Results: PCa was detected in 98 patients (94%) with acceptable variability between readers. There was a significantly higher visual score and TBR in positive lobes compared with tumor-negative lobes. Receiver-operating characteristic analysis showed that visual scores more accurately discriminated lobes with GS ≤ 3 + 3 from ≥ 3 + 4, whereas TBRs discriminated high-grade disease from normal lobes better. Visual scores and TBRs correlated significantly with GS. 99mTc-trofolastat SPECT/CT detected LNI with a sensitivity of 50% and specificity of 87%, and TBR values significantly predicted LNI with a sensitivity of 90%. Conclusion: 99mTc-trofolastat SPECT/CT detects PCa with high sensitivity in patients with intermediate- and high-risk PCa compared with histology. It has the potential to be used as a surrogate marker for GS and predict LNI.

    更新日期:2017-09-05
  • Expression of Gastrin-Releasing Peptide Receptor in Breast Cancer and Its Association with Pathologic, Biologic, and Clinical Parameters: A Study of 1,432 Primary Tumors
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    Clément Morgat; Gaétan MacGrogan; Véronique Brouste; Valérie Vélasco; Nicolas Sévenet; Hervé Bonnefoi; Philippe Fernandez; Marc Debled; Elif Hindié

    A growing body of evidence suggests that gastrin-releasing peptide receptor (GRPR) might be a valuable target in breast cancer. To understand which patients can be potential candidates for GRPR-based imaging or targeted therapy, we screened invasive breast cancers by immunohistochemistry for the presence and intensity of GRPR expression. Methods: We explored a tissue microarray of 1,432 primary breast tumors from patients who underwent surgery between 2000 and 2005 at Institut Bergonié, without prior neoadjuvant treatment. We studied associations between GRPR expression and clinical, pathologic, and biologic parameters. The association between GRPR expression and distant metastasis-free interval was also examined. Results: GRPR overexpression was found in 75.8% of the 1,432 tumors and was most strongly associated with estrogen receptor (ER) positivity (GRPR was high in 83.2% of ER-positive and 12% of ER-negative tumors; P < 0.00001). When molecular subtypes of breast cancer were considered, GRPR was overexpressed in 86.2% of luminal A–like tumors, 70.5% of luminal B–like human epidermal growth factor receptor 2 (HER2)–negative tumors, 82.8% of luminal B–like HER2-positive tumors, 21.3% of HER2-enriched tumors, and 7.8% of triple-negative tumors. Importantly, when breast tumors overexpressed GRPR, high GRPR expression was also found in metastatic lymph nodes in 94.6% of cases. Primary tumors with high GRPR expression were associated with lower risk of distant metastases at follow-up in univariate analysis (Log-rank P = 0.0084) but not in multivariate analysis. Hence, the prognostic impact of GRPR was lost when examined within specific molecular subtypes. Conclusion: Because GRPR is overexpressed in a high percentage of ER-positive tumors, GRPR targeting offers wide perspectives for imaging and treatment in patients with ER-positive breast cancer, using recently developed radiolabeled GRPR ligands.

    更新日期:2017-09-05
  • Cerenkov Radiation–Induced Photoimmunotherapy with 18F-FDG
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    Yuko Nakamura; Tadanobu Nagaya; Kazuhide Sato; Shuhei Okuyama; Fusa Ogata; Karen Wong; Stephen Adler; Peter L. Choyke; Hisataka Kobayashi

    Near-infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with toxicity induced by photoabsorbers after irradiation with NIR light. A limitation of NIR-PIT is the inability to deliver NIR light to a tumor located deep inside the body. Cerenkov radiation (CR) is the ultraviolet and blue light that is produced by a charged particle traveling through a dielectric medium faster than the speed of light in that medium and is commonly produced during radioactive decay. Here, we demonstrate the feasibility of using CR generated by 18F-FDG accumulated in tumors to induce photoimmunotherapy. Methods: Using A431-luc cells, we evaluated the therapeutic effects of CR-PIT in vitro and in vivo using bioluminescence imaging. Results: CR-PIT showed significant suppression of tumor size, but the decrease of bioluminescence after CR-PIT was not observed consistently over the entire time course. Conclusion: Although CR-PIT can induce tumor killing deep within body, it is less effective than NIR-PIT, possibly related to the relatively lower efficiency of short wavelength light than NIR.

    更新日期:2017-09-05
  • 89Zr-DFO-AMG102 Immuno-PET to Determine Local Hepatocyte Growth Factor Protein Levels in Tumors for Enhanced Patient Selection
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    Eric W. Price; Kathryn E. Carnazza; Sean D. Carlin; Andrew Cho; Kimberly J. Edwards; Kuntal K. Sevak; Jonathan M. Glaser; Elisa de Stanchina; Yelena Y. Janjigian; Jason S. Lewis

    The hepatocyte growth factor (HGF) binding antibody rilotumumab (AMG102) was modified for use as a 89Zr-based immuno-PET imaging agent to noninvasively determine the local levels of HGF protein in tumors. Because recent clinical trials of HGF-targeting therapies have been largely unsuccessful in several different cancers (e.g., gastric, brain, lung), we have synthesized and validated 89Zr-DFO-AMG102 as a companion diagnostic for improved identification and selection of patients having high local levels of HGF in tumors. To date, patient selection has not been performed using the local levels of HGF protein in tumors. Methods: The chelator p-SCN-Bn-DFO was conjugated to AMG102, radiolabeling with 89Zr was performed in high radiochemical yields and purity (>99%), and binding affinity of the modified antibody was confirmed using an enzyme-linked immunosorbent assay (ELISA)–type binding assay. PET imaging, biodistribution, autoradiography and immunohistochemistry, and ex vivo HGF ELISA experiments were performed on murine xenografts of U87MG (HGF-positive, MET-positive) and MKN45 (HGF-negative, MET-positive) and 4 patient-derived xenografts (MET-positive, HGF unknown). Results: Tumor uptake of 89Zr-DFO-AMG102 at 120 h after injection in U87MG xenografts (HGF-positive) was high (36.8 ± 7.8 percentage injected dose per gram [%ID/g]), whereas uptake in MKN45 xenografts (HGF-negative) was 5.0 ± 1.3 %ID/g and a control of nonspecific human IgG 89Zr-DFO-IgG in U87MG tumors was 11.5 ± 3.3 %ID/g, demonstrating selective uptake in HGF-positive tumors. Similar experiments performed in 4 different gastric cancer patient-derived xenograft models showed low uptake of 89Zr-DFO-AMG102 (∼4–7 %ID/g), which corresponded with low HGF levels in these tumors (ex vivo ELISA). Autoradiography, immunohistochemical staining, and HGF ELISA assays confirmed that elevated levels of HGF protein were present only in U87MG tumors and that 89Zr-DFO-AMG102 uptake was closely correlated with HGF protein levels in tumors. Conclusion: The new immuno-PET imaging agent 89Zr-DFO-AMG102 was successfully synthesized, radiolabeled, and validated in vitro and in vivo to selectively accumulate in tumors with high local levels of HGF protein. These results suggest that 89Zr-DFO-AMG102 would be a valuable companion diagnostic tool for the noninvasive selection of patients with elevated local concentrations of HGF in tumors for planning any HGF-targeted therapy, with the potential to improve clinical outcomes.

    更新日期:2017-09-05
  • Brachytherapy with Intratumoral Injections of Radiometal-Labeled Polymers That Thermoresponsively Self-Aggregate in Tumor Tissues
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    Kohei Sano; Yuko Kanada; Kengo Kanazaki; Ning Ding; Masahiro Ono; Hideo Saji

    Brachytherapy is a type of radiotherapy wherein titanium capsules containing therapeutic radioisotopes are implanted within tumor tissues, enabling high-dose radioirradiation to tumor tissues around the seeds. Although marked therapeutic effects have been demonstrated, brachytherapy needs a complicated implantation technique under general anesthesia and the seeds could migrate to other organs. The aim of this study was to establish a novel brachytherapy using biocompatible, injectable thermoresponsive polymers (polyoxazoline [POZ]) labeled with 90Y, which can self-aggregate above a specific transition temperature (Tt), resulting in long-term intratumoral retention of radioactivity and therapeutic effect. Therefore, we evaluated the tumor retention of radiolabeled POZ derivatives and their therapeutic effects. Methods: Using oxazoline derivatives with ethyl (Et), isopropyl (Isp), and propyl (Pr) side chains, we synthesized EtPOZ, IspPOZ, Isp-PrPOZ (heteropolymer), and PrPOZ and measured their characteristic Tts. The intratumoral retention of 111In-labeled POZ was evaluated until 7 d after injection in nude mice bearing PC-3 human prostate cancer. The intratumoral localization of 111In-labeled POZ derivatives was investigated by an autoradiographic study. Furthermore, a therapeutic study using 90Y-labeled Isp-PrPOZ was performed, and tumor growth and survival rate were evaluated. Results: The Tts of EtPOZ, IspPOZ, Isp-PrPOZ, and PrPOZ (∼20 kDa) were greater than 70°C, 34°C, 25°C, and 19°C, respectively. In the intratumoral injection study, Isp-PrPOZ and PrPOZ (2,000 μM) with Tts lower than tumor temperature (33.5°C under anesthesia) showed a significantly higher retention of radioactivity at 1 d after injection (73.6% and 73.9%, respectively) than EtPOZ (5.6%) and IspPOZ (15.8%). Even at low injected dose (100 μM), Isp-PrPOZ exhibited high retention (68.3% at 1 d). The high level of radioactivity of Isp-PrPOZ was retained in the tumor 7 d after injection (69.5%). The autoradiographic study demonstrated that the radioactivity of 111In-labeled Isp-PrPOZ and PrPOZ was localized in a small area. In the therapeutic study using 90Y-labeled Isp-PrPOZ, significant suppression of tumor growth and prolonged survival rate were achieved in an injection dose–dependent manner compared with that observed for the vehicle-injected group and nonradioactive Isp-PrPOZ–injected group. Conclusion: The injectable 90Y-labeled Isp-PrPOZ was retained for a prolonged period within tumor tissues via self-aggregation and exhibited marked therapeutic effect, suggesting its usefulness for brachytherapy.

    更新日期:2017-09-05
  • Diagnostic PET Imaging of Mammary Microcalcifications Using 64Cu-DOTA-Alendronate in a Rat Model of Breast Cancer
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    Bradley J. Ahrens; Lin Li; Alexandra K. Ciminera; Junie Chea; Erasmus Poku; James R. Bading; Michael R. Weist; Marcia M. Miller; David M. Colcher; John E. Shively

    The development of improved breast cancer screening methods is hindered by a lack of cancer-specific imaging agents and effective small-animal models to test them. The purpose of this study was to evaluate 64Cu-DOTA-alendronate as a mammary microcalcification-targeting PET imaging agent, using an ideal rat model. Our long-term goal is to develop 64Cu-DOTA-alendronate for the detection and noninvasive differentiation of malignant versus benign breast tumors with PET. Methods: DOTA-alendronate was synthesized, radiolabeled with 64Cu, and administered to normal or tumor-bearing aged, female, retired breeder Sprague–Dawley rats for PET imaging. Mammary tissues were subsequently labeled and imaged with light, confocal, and electron microscopy to verify microcalcification targeting specificity of DOTA-alendronate and elucidate the histologic and ultrastructural characteristics of the microcalcifications in different mammary tumor types. Tumor uptake, biodistribution, and dosimetry studies were performed to evaluate the efficacy and safety of 64Cu-DOTA-alendronate. Results: 64Cu-DOTA-alendronate was radiolabeled with a 98% yield. PET imaging using aged, female, retired breeder rats showed specific binding of 64Cu-DOTA-alendronate in mammary glands and mammary tumors. The highest uptake of 64Cu-DOTA-alendronate was in malignant tumors and the lowest uptake in benign tumors and normal mammary tissue. Confocal analysis with carboxyfluorescein-alendronate confirmed the microcalcification binding specificity of alendronate derivatives. Biodistribution studies revealed tissue alendronate concentrations peaking within the first hour, then decreasing over the next 48 h. Our dosimetric analysis demonstrated a 64Cu effective dose within the acceptable range for clinical PET imaging agents and the potential for translation into human patients. Conclusion: 64Cu-DOTA-alendronate is a promising PET imaging agent for the sensitive and specific detection of mammary tumors as well as the differentiation of malignant versus benign tumors based on absolute labeling uptake.

    更新日期:2017-09-05
  • Functional Optical Imaging of Primary Human Tumor Organoids: Development of a Personalized Drug Screen
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    Alex J. Walsh; Rebecca S. Cook; Melissa C. Skala

    Primary tumor organoids are a robust model of individual human cancers and present a unique platform for patient-specific drug testing. Optical imaging is uniquely suited to assess organoid function and behavior because of its subcellular resolution, penetration depth through the entire organoid, and functional endpoints. Specifically, optical metabolic imaging (OMI) is highly sensitive to drug response in organoids, and OMI in tumor organoids correlates with primary tumor drug response. Therefore, an OMI organoid drug screen could enable accurate testing of drug response for individualized cancer treatment. The objective of this perspective is to introduce OMI and tumor organoids to a general audience in order to foster the adoption of these techniques in diverse clinical and laboratory settings.

    更新日期:2017-09-05
  • Operational and Dosimetric Aspects of Pediatric PET/CT
    J Nucl. Med. (IF 6.646) Pub Date : 2017-09-01
    Frederic H. Fahey; Alison Goodkind; Robert D. MacDougall; Leah Oberg; Sonja I. Ziniel; Richard Cappock; Michael J. Callahan; Neha Kwatra; S. Ted Treves; Stephan D. Voss

    No consistent guidelines exist for the acquisition of a CT scan as part of pediatric PET/CT. Given that children may be more vulnerable to the effects of ionizing radiation, it is necessary to develop methods that provide diagnostic-quality imaging when needed, in the shortest time and with the lowest patient radiation exposure. This article describes the basics of CT dosimetry and PET/CT acquisition in children. We describe the variability in pediatric PET/CT techniques, based on a survey of 19 PET/CT pediatric institutions in North America. The results of the survey demonstrated that, although most institutions used automatic tube current modulation, there remained a large variation of practice, on the order of a factor of 2–3, across sites, pointing to the need for guidelines. We introduce the approach developed at our institution for using a multiseries PET/CT acquisition technique that combines diagnostic-quality CT in the essential portion of the field of view and a low-dose technique to image the remainder of the body. This approach leads to a reduction in radiation dose to the patient while combining the PET and the diagnostic CT into a single acquisition. The standardization of pediatric PET/CT provides an opportunity for a reduction in the radiation dose to these patients while maintaining an appropriate level of diagnostic image quality.

    更新日期:2017-09-05
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
所有期刊列表A-Z