Doss Mohan, Kolb Hartmuth C, Walsh Joseph C, Mocharla Vani P, Zhu Zhihong, Haka Michael, Alpaugh R Katherine, Chen David Y T, Yu Jian Q
Diagnostic Imaging, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111-2497, USA.
Mol Imaging Biol. 2014 Oct;16(5):739-46. doi: 10.1007/s11307-014-0730-7.
[(18) F]VM4-037 has been developed as a positron emission tomography (PET) imaging marker to detect carbonic anhydrase IX (CA-IX) overexpression and is being investigated for use as a surrogate marker for tissue hypoxia. The purpose of this study was to determine the biodistribution and estimate the radiation dose from [(18) F]VM4-037 using whole-body PET/CT scans in healthy human volunteers.
Successive whole-body PET/CT scans were performed after intravenous injection of [(18) F]VM4-037 in four healthy humans. The radiotracer uptakes in different organs were determined from the analysis of the PET scans. Human radiation doses were estimated using OLINDA/EXM software.
High uptake of [(18) F]VM4-037 was observed in the liver and kidneys, with little clearance of activity during the study period, with mean standardized uptake values of ~35 in liver and ~22 in kidneys at ~1 h after injection. The estimated effective dose was 28 ± 1 μSv/MBq and the absorbed doses for the kidneys and liver were 273 ± 31 and 240 ± 68 μGy/MBq, respectively, for the adult male phantom. Hence, the effective dose would be 10 ± 0.5 mSv for the anticipated injected activity of 370 MBq, and the kidney and liver doses would be 101 ± 11 and 89 ± 25 mGy, respectively.
[(18) F]VM4-037 displayed very high uptake in the liver and kidneys with little clearance of activity during the study period, resulting in these organs receiving the highest radiation doses among all bodily organs. Though the effective dose and the organ doses are within the limits considered as safe, the enhanced uptake of [(18) F]VM4-037 in the kidneys and liver will make the compound unsuitable for imaging overexpression of CA-IX in those two organs. However, the tracer may be suitable for imaging overexpression of CA-IX in lesions in other regions of the body such as in the lungs or head and neck region.
[（18）F]VM4 - 037已被开发为一种正电子发射断层扫描（PET）成像标记物，用于检测碳酸酐酶IX（CA - IX）的过表达，并且正在作为组织缺氧的替代标记物进行研究。本研究的目的是通过对健康人类志愿者进行全身PET/CT扫描来确定[（18）F]VM4 - 037的生物分布并估算其辐射剂量。
对四名健康人静脉注射[（18）F]VM4 - 037后进行连续的全身PET/CT扫描。通过对PET扫描的分析确定不同器官中的放射性示踪剂摄取情况。使用OLINDA/EXM软件估算人体辐射剂量。
在肝脏和肾脏中观察到[（18）F]VM4 - 037的高摄取，在研究期间活性清除很少，注射后约1小时肝脏中的平均标准化摄取值约为35，肾脏中约为22。对于成年男性体模，估计有效剂量为28±1μSv/MBq，肾脏和肝脏的吸收剂量分别为273±31和240±68μGy/MBq。因此，对于预期注射活度370MBq，有效剂量将为10±0.5mSv，肾脏和肝脏剂量分别为101±11和89±25mGy。
[（18）F]VM4 - 037在肝脏和肾脏中显示出非常高的摄取，在研究期间活性清除很少，导致这些器官在所有身体器官中接受最高的辐射剂量。虽然有效剂量和器官剂量在被认为是安全的限度内，但[（18）F]VM4 - 037在肾脏和肝脏中的摄取增加将使该化合物不适用于对这两个器官中CA - IX的过表达进行成像。然而，该示踪剂可能适用于对身体其他区域如肺部或头颈部区域病变中CA - IX的过表达进行成像。
