Radiolabeled prostate-specific membrane antigen (PSMA) PET has demonstrated promising results for prostate cancer (PCa) imaging. Quantification of PSMA radiotracer uptake is desired as it enables reliable interpretation of PET images, use of PSMA uptake as an imaging biomarker for tumor characterization, and evaluation of treatment effects. The aim of this study was to perform a full pharmacokinetic analysis of 2-(3-(1-carboxy-5-[(6-¹⁸F-fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid (¹⁸F-DCFPyL), a second-generation ¹⁸F-labeled PSMA ligand. On the basis of the pharmacokinetic analysis (reference method), simplified methods for quantification of ¹⁸F-DCFPyL uptake were validated. Methods: Eight patients with metastasized PCa were included. Dynamic PET acquisitions were performed at 0–60 and 90–120 min after injection of a median dose of 313 MBq of ¹⁸F-DCFPyL (range, 292–314 MBq). Continuous and manual arterial blood sampling provided calibrated plasma tracer input functions. Time–activity curves were derived for each PCa metastasis, and ¹⁸F-DCFPyL kinetics were described using standard plasma input tissue-compartment models. Simplified methods for quantification of ¹⁸F-DCFPyL uptake (SUVs; tumor-to-blood ratios [TBRs]) were correlated with kinetic parameter estimates obtained from full pharmacokinetic analysis. Results: In total, 46 metastases were evaluated. A reversible 2-tissue-compartment model was preferred for ¹⁸F-DCFPyL kinetics in 59% of the metastases. The observed k₄ was small, however, resulting in nearly irreversible kinetics during the course of the PET study. Hence, k₄ was fixated (0.015) and net influx rate, K_i, was preferred as the reference kinetic parameter. Whole-blood TBR provided an excellent correlation with K_i from full kinetic analysis (R² = 0.97). This TBR could be simplified further by replacing the blood samples with an image-based, single measurement of blood activity in the ascending aorta (image-based TBR, R² = 0.96). SUV correlated poorly with K_i (R² = 0.47 and R² = 0.60 for SUV normalized to body weight and lean body mass, respectively), most likely because of deviant blood activity concentrations (i.e., tumor tracer input) in patients with higher tumor volumes. Conclusion: ¹⁸F-DCFPyL kinetics in PCa metastases are best described by a reversible 2-tissue-compartment model. Image-based TBRs were validated as a simplified method to quantify ¹⁸F-DCFPyL uptake and might be applied to clinical, whole-body PET scans. SUV does not provide reliable quantification of ¹⁸F-DCFPyL uptake.

放射性标记的前列腺特异性膜抗原（PSMA）PET对前列腺癌（PCa）成像已显示出令人鼓舞的结果。希望对PSMA放射性示踪剂的摄取进行量化，因为它能够可靠地解释PET图像，将PSMA摄取用作肿瘤表征的成像生物标记，并评估治疗效果。这项研究的目的是对2-（3-（1-羧基-5-[（6- ¹⁸ F-氟吡啶-3-羰基）-氨基]-戊基）-脲基）-进行完整的药代动力学分析戊二酸（¹⁸ F-DCFPyL），第二代¹⁸ F标记的PSMA配体。在药代动力学分析（参考方法）的基础上，验证了定量¹⁸ F-DCFPyL摄取的简化方法。方法：包括转移性PCa的8例患者。注射¹⁸ F-DCFPyL的中位剂量313 MBq （范围为292-314 MBq）后，在0-60和90-120分钟进行动态PET采集。连续和手动动脉血液采样提供了校准的血浆示踪剂输入功能。得出了每个PCa转移的时间-活动曲线，并使用标准血浆输入组织室模型描述了¹⁸ F-DCFPyL动力学。量化¹⁸ F-DCFPyL摄取的简化方法（SUV；肿瘤与血液的比率[TBR]）与从完整药代动力学分析获得的动力学参数估计值相关。结果：总共评估了46个转移灶。首选可逆的2组织隔室模型¹⁸ F-DCFPyL动力学的转移率为59％。然而，观察到的k ₄很小，导致在PET研究过程中几乎不可逆的动力学。因此，k ₄固定为（0.015），净流入率K _i优选作为参考动力学参数。通过全动力学分析，全血TBR与K _i具有极好的相关性（R ² = 0.97）。通过用基于图像的升主动脉血液活动的单个测量值代替血样，可以进一步简化此TBR（基于图像的TBR，R ² = 0.96）。SUV与K _i（R分别归一化为体重和瘦体重的SUV的² = 0.47和R ² = 0.60），最可能的原因是肿瘤体积较大的患者血液活动浓度异常（即，肿瘤示踪剂输入）。结论： PCa转移中的¹⁸ F-DCFPyL动力学最好由可逆的2组织室模型描述。基于图像的TBR已被验证为定量¹⁸ F-DCFPyL摄取的简化方法，可用于临床全身PET扫描。SUV无法提供¹⁸ F-DCFPyL摄入量的可靠定量。