Biodistribution and radiation dosimetry of the carbonic anhydrase IX imaging agent [(18) F]VM4-037 determined from PET/CT scans in healthy volunteers

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00884520.

Conflict of interest statement

Conflict of Interest Statement

Joseph C. Walsh and Zhihong Zhu are employees of Siemens Molecular Imaging Inc. Hartmuth C. Kolb, Vani P. Mocharla, and Michael Haka were previously employees of Siemens Molecular Imaging Inc. at the time of the work described here. Fox Chase Cancer Center performed the research work described in this paper under a research contract with Siemens Molecular Imaging Inc. None of the authors received any additional compensation for performing this work.

Figures

FIGURE 1.

Chemical structure of [18F]VM4–037

FIGURE 2.

Synthesis of [18F]VM4–037

FIGURE 3.

Decay-corrected anterior maximum-intensity projections of PET at 10, 60, 86, 113, and 133 min (from left to right) after injection of [18F]VM4–037 in a female subject. There is little clearance of activity through the renal system, and there is high uptake of activity in liver and kidneys.

FIGURE 4.

Mean percent administered activity and SD for top 3 organs determined on basis of four [18F]VM4–037 PET emission scans in human volunteers, as a function of time after injection. Little clearance of activity was observed in the organs.