Department of Nuclear Medicine, University Hospital Leipzig, 04103 Leipzig, Germany.
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, 04318 Leipzig, Germany.
Molecules. 2020 Apr 26;25(9):2024. doi: 10.3390/molecules25092024.
Overexpression of monocarboxylate transporters (MCTs) has been shown for a variety of human cancers (e.g., colon, brain, breast, and kidney) and inhibition resulted in intracellular lactate accumulation, acidosis, and cell death. Thus, MCTs are promising targets to investigate tumor cancer metabolism with positron emission tomography (PET). Here, the organ doses (ODs) and the effective dose (ED) of the first F-labeled MCT1/MCT4 inhibitor were estimated in juvenile pigs. Whole-body dosimetry was performed in three piglets (age: ~6 weeks, weight: ~13-15 kg). The animals were anesthetized and subjected to sequential hybrid Positron Emission Tomography and Computed Tomography (PET/CT) up to 5 h after an intravenous (iv) injection of 156 ± 54 MBq [F]FACH. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time-activity data. Time and mass scales were adapted to the human order of magnitude and the ODs calculated using the ICRP 89 adult male phantom with OLINDA 2.1. The ED was calculated using tissue weighting factors as published in Publication 103 of the International Commission of Radiation Protection (ICRP103). The highest organ dose was received by the urinary bladder (62.6 ± 28.9 µSv/MBq), followed by the gall bladder (50.4 ± 37.5 µSv/MBq) and the pancreas (30.5 ± 27.3 µSv/MBq). The highest contribution to the ED was by the urinary bladder (2.5 ± 1.1 µSv/MBq), followed by the red marrow (1.7 ± 0.3 µSv/MBq) and the stomach (1.3 ± 0.4 µSv/MBq). According to this preclinical analysis, the ED to humans is 12.4 µSv/MBq when applying the ICRP103 tissue weighting factors. Taking into account that preclinical dosimetry underestimates the dose to humans by up to 40%, the conversion factor applied for estimation of the ED to humans would rise to 20.6 µSv/MBq. In this case, the ED to humans upon an iv application of ~300 MBq [F]FACH would be about 6.2 mSv. This risk assessment encourages the translation of [F]FACH into clinical study phases and the further investigation of its potential as a clinical tool for cancer imaging with PET.
单羧酸转运蛋白（MCTs）的过表达已在多种人类癌症中得到证实（例如，结肠癌、脑癌、乳腺癌和肾癌），抑制 MCTs 会导致细胞内乳酸积累、酸中毒和细胞死亡。因此，MCTs 是研究肿瘤代谢的有希望的靶点，可以用正电子发射断层扫描（PET）进行研究。在此，研究人员在幼年猪中评估了首例 F 标记的 MCT1/MCT4 抑制剂的器官剂量（OD）和有效剂量（ED）。在三只小猪（年龄：约 6 周，体重：约 13-15 公斤）中进行了全身剂量测定。动物被麻醉，并在静脉（iv）注射 156 ± 54 MBq [F]FACH 后进行连续的混合正电子发射断层扫描和计算机断层扫描（PET/CT），直至 5 小时。通过感兴趣区域定义所有相关器官。根据时间-活性数据拟合指数曲线。时间和质量标度适应人体数量级，使用 OLINDA 2.1 中的 ICRP 89 成年男性体模计算 OD。使用国际辐射防护委员会（ICRP）第 103 号出版物中公布的组织权重因子计算 ED。膀胱（62.6 ± 28.9 µSv/MBq）接受的器官剂量最高，其次是胆囊（50.4 ± 37.5 µSv/MBq）和胰腺（30.5 ± 27.3 µSv/MBq）。对 ED 贡献最大的是膀胱（2.5 ± 1.1 µSv/MBq），其次是红骨髓（1.7 ± 0.3 µSv/MBq）和胃（1.3 ± 0.4 µSv/MBq）。根据这项临床前分析，如果应用 ICRP103 组织权重因子，人类的 ED 为 12.4 µSv/MBq。考虑到临床前剂量测定低估了人体剂量的 40%左右，因此用于估计人类 ED 的转换因子将上升至 20.6 µSv/MBq。在这种情况下，静脉内应用约 300 MBq [F]FACH 后，人类的 ED 约为 6.2 mSv。这种风险评估鼓励将 [F]FACH 转化为临床研究阶段，并进一步研究其作为癌症 PET 成像的临床工具的潜力。
