18F-ICMT-11, a Caspase-3-Specific PET Tracer for Apoptosis: Biodistribution and Radiation Dosimetry

Effective anticancer therapy induces tumor cell death through apoptosis. Noninvasive monitoring of apoptosis during therapy may provide predictive outcome information and help tailor treatment. A caspase-3-specific imaging radiotracer, F-18-(S)-1-((1-(2-fluoroethyl)-1H-[1,2,3]-triazol-4-yl)methyl)-5-(2(2,4-difluorophenoxymethyl)-pyrrolidine-1-sulfonyl)isatin (F-18-ICMT-11), has been developed for use in PET studies. We report the safety, biodistribution, and internal radiation dosimetry profiles of F-18-ICMT-11 in 8 healthy human volunteers. Methods: F-18-ICMT-11 was intravenously administered as a bolus injection (mean +/- SD, 159 +/- 2.75 MBq; range, 154-161 MBq) to 8 healthy volunteers (4 men, 4 women). Whole-body (vertex to mid thigh) PET/CT scans were acquired at 6 time points, up to 4 h after tracer injection. Serial whole blood, plasma, and urine samples were collected for radioactivity measurement and radiotracer stability. In vivo F-18 activities were determined from quantitative analysis of the images, and time-activity curves were generated. The total numbers of disintegrations in each organ normalized to injected activity (residence times) were calculated as the area under the curve of the time-activity curve, normalized to injected activities and standard values of organ volumes. Dosimetry calculations were then performed using OLINDA/EXM 1.1. Results: Injection of F-18-ICMT-11 was well tolerated in all subjects, with no serious tracer-related adverse events reported. The mean effective dose averaged over both men and women was estimated to be 0.025 +/- 0.004 mSv/MBq (men, 0.022 +/- 0.004 mSv/MBq; women, 0.027 +/- 0.004 mSv/MBq). The 5 organs receiving the highest absorbed dose (mGy/MBq), averaged over both men and women, were the gallbladder wall (0.59 +/- 0.44), small intestine (0.12 +/- 0.05), upper large intestinal wall (0.08 +/- 0.07), urinary bladder wall (0.08 +/- 0.02), and liver (0.07 +/- 0.01). Elimination was both renal and via the hepatobiliary system. Conclusion: F-18-ICMT-11 is a safe PET tracer with a dosimetry profile comparable to other common F-18 PET tracers. These data support the further development of F-18-ICMT-11 for clinical imaging of apoptosis.