Purpose

Non-invasive imaging is a key clinical tool for detection and treatment monitoring of infections. Existing clinical imaging techniques are frequently unable to distinguish infection from tumors or sterile inflammation. This challenge is well-illustrated by prosthetic joint infections that often complicate joint replacements. D-methyl-¹¹C-methionine (D-¹¹C-Met) is a new bacteria-specific PET radiotracer, based on an amino acid D-enantiomer, that is rapidly incorporated into the bacterial cell wall. In this manuscript, we describe the biodistribution, radiation dosimetry, and initial human experience using D-¹¹C-Met in patients with suspected prosthetic joint infections.

Methods

614.5 ± 100.2 MBq of D-¹¹C-Met was synthesized using an automated in-loop radiosynthesis method and administered to six healthy volunteers and five patients with suspected prosthetic joint infection, who were studied by PET/MRI. Time-activity curves were used to calculate residence times for each source organ. Absorbed doses to each organ and body effective doses were calculated using OLINDA/EXM 1.1 with both ICRP 60 and ICRP 103 tissue weighting factors. SUV_max and SUV_peak were calculated for volumes of interest (VOIs) in joints with suspected infection, the unaffected contralateral joint, blood pool, and soft tissue background. A two-tissue compartment model was used for kinetic modeling.

Results

D-¹¹C-Met was well tolerated in all subjects. The tracer showed clearance from both urinary (rapid) and hepatobiliary (slow) pathways as well as low effective doses. Moreover, minimal background was observed in both organs with resident micro-flora and target organs, such as the spine and musculoskeletal system. Additionally, D-¹¹C-Met showed increased focal uptake in areas of suspected infection, demonstrated by a significantly higher SUV_max and SUV_peak calculated from VOIs of joints with suspected infections compared to the contralateral joints, blood pool, and background (P < 0.01). Furthermore, higher distribution volume and binding potential were observed in suspected infections compared to the unaffected joints.

Conclusion

D-¹¹C-Met has a favorable radiation profile, minimal background uptake, and fast urinary extraction. Furthermore, D-¹¹C-Met showed increased uptake in areas of suspected infection, making this a promising approach. Validation in larger clinical trials with a rigorous gold standard is still required.

中文翻译：

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使用 D-甲基-11C-蛋氨酸 PET/MRI 对关节感染进行成像：人类的初步经验

目的

无创成像是检测和治疗感染监测的关键临床工具。现有的临床成像技术经常无法区分感染与肿瘤或无菌炎症。假体关节感染很好地说明了这一挑战，这通常使关节置换复杂化。D-甲基- ¹¹ C-蛋氨酸 (D- ¹¹ C-Met) 是一种新的细菌特异性 PET 放射性示踪剂，基于氨基酸 D-对映异构体，可迅速掺入细菌细胞壁。在这份手稿中，我们描述了在疑似假关节感染患者中使用 D- ¹¹ C-Met的生物分布、辐射剂量测定和最初的人类经验。

方法

使用自动环内放射合成方法合成614.5 ± 100.2 MBq 的 D - ¹¹ C-Met，并给予 6 名健康志愿者和 5 名疑似假体关节感染的患者，这些患者通过 PET/MRI 进行研究。时间-活动曲线用于计算每个源器官的停留时间。使用 OLINDA/EXM 1.1 和 ICRP 60 和 ICRP 103 组织加权因子计算每个器官的吸收剂量和身体有效剂量。计算疑似感染关节、未受影响的对侧关节、血池和软组织背景中的感兴趣体积 (VOI) 的SUV_最大值和 SUV_峰值。使用双组织隔室模型进行动力学建模。

结果

D - ¹¹ C-Met 在所有受试者中都具有良好的耐受性。示踪剂显示从尿（快速）和肝胆（慢）通路以及低有效剂量的清除。此外，在具有常驻微生物区系的器官和靶器官（例如脊柱和肌肉骨骼系统）中都观察到最小的背景。此外，D - ¹¹ C-Met 显示疑似感染区域的局灶性摄取增加，与对侧关节、血池和背景相比，根据疑似感染关节的 VOI 计算得出的SUV_最大值和 SUV_峰值显着更高（ P < 0.01)。此外，与未受影响的关节相比，在疑似感染中观察到更高的分布体积和结合潜力。

结论

D - ¹¹ C-Met 具有良好的辐射分布、最小的背景吸收和快速的尿液提取。此外，D - ¹¹ C-Met 显示在疑似感染区域的摄取增加，使其成为一种有前途的方法。仍然需要在具有严格金标准的大型临床试验中进行验证。