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

Abstract

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, 18 F-, has been developed for use in PET studies. We report the safety, biodistribution, and internal radiation dosimetry profiles of 18 F-ICMT-11 in 8 healthy human volunteers. Methods: 18 F-ICMT-11 was intravenously administered as a bolus injection (mean 6 SD, 159 6 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 18 F 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 18 F-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 6 0.004 mSv/MBq (men, 0.022 6 0.004 mSv/MBq; women, 0.027 6 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 6 0.44), small intestine (0.12 6 0.05), upper large intestinal wall (0.08 6 0.07), urinary bladder wall (0.08 6 0.02), and liver (0.07 6 0.01). Elimination was both renal and via the hepatobiliary system. Conclusion: 18 F-ICMT-11 is a safe PET tracer with a dosimetry profile comparable to other common 18 F PET tracers. These data support the further development of 18 F-ICMT-11 for clinical imaging of apoptosis.

Rapid Imaging of Tumor Cell Death In Vivo Using the C2A Domain of Synaptotagmin-I

“…However, the clinical utility of duramycin has yet to be demonstrated. Imaging agents that target CC3, an executioner caspase in the apoptosis pathway, have also been developed for detection of cell death in vivo (25), and a probe capable of detecting CC3 has progressed to clinical trials (32). However, because CC3 is a transient biomarker of cell death, the choice of temporal imaging window after treatment is critical (33).…”

Biodistribution and Radiation Dosimetry of Deuterium-Substituted 18F-Fluoromethyl-[1, 2-2H4]Choline in Healthy Volunteers

“…The collection of safety data, image acquisition, image analysis, measurement of blood and urine radioactivity, and the dosimetry calculations were performed as previously described (16). Table 1 describes the image acquisition protocol.…”

Whole-Body Radiation Dosimetry of 11C-Carbonyl-URB694: A PET Tracer for Fatty Acid Amide Hydrolase

“…1) and the rapid metabolism of O-arylcarbamates compounds (i.e., CURB/URB694) where half of the parent compound is metabolized in the first 20 m after injection (8). The gallbladder timeactivity curve is not uniformly reported in other dosimetry papers but is not unique to 11 C-CURB (18,19). The large variance in gallbladder uptake of radioactivity observed is attributed to variable hepatobiliary clearance and gallbladder emptying among the subjects.…”