Biodistribution and Radiation Dosimetry of the Carbonic Anhydrase IX Imaging Agent [18 F]VM4-037 Determined from PET/CT Scans in Healthy Volunteers

• Published in: Molecular imaging and biology Vol. 16; no. 5; pp. 739 - 746
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.10.2014; Springer Nature B.V
• Subjects: Adult; Aged; Antigens, Neoplasm - metabolism; Carbonic Anhydrase IX; Carbonic Anhydrases - metabolism; Dipeptides - chemical synthesis; Dipeptides - chemistry; Dipeptides - pharmacokinetics; Female; Healthy Volunteers; Humans; Imaging; Male; Medicine; Medicine & Public Health; Middle Aged; Positron-Emission Tomography; Radiology; Radiometry; Research Article; Sulfonamides - chemical synthesis; Sulfonamides - chemistry; Sulfonamides - pharmacokinetics; Tissue Distribution; Tomography, X-Ray Computed; Carbonic anhydrase IX; [; Biodistribution; Internal dosimetry; PET; F]VM4-037
• ISSN: 1536-1632; 1860-2002
• DOI: 10.1007/s11307-014-0730-7

Purpose [ 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. Procedures 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. Results 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. Conclusions [ 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.