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18F-ICMT-11, a caspase-3-specific PET tracer for apoptosis: biodistribution and radiation dosimetry
Amarnath Challapalli1, Laura M Kenny, William A Hallett
1Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
Unlabelled:
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-(S)-1-((1-(2-fluoroethyl)-1H-[1,2,3]-triazol-4-yl)methyl)-5-(2(2,4-difluorophenoxymethyl)-pyrrolidine-1-sulfonyl)isatin ((18)F-ICMT-11), 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 ± 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 (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 ± 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:
(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.
Insights
The novel PET tracer (18)F-ICMT-11, which images apoptosis, demonstrated a favorable safety and dosimetry profile in healthy volunteers. These findings support its clinical use for monitoring cancer therapy response.
Area of Science:
- Oncology
- Nuclear Medicine
- Radiochemistry
Background:
- Effective anticancer therapies induce tumor cell death via apoptosis.
- Noninvasive monitoring of apoptosis can predict treatment outcomes and guide therapy adjustments.
- A novel caspase-3-specific PET imaging radiotracer, (18)F-ICMT-11, has been developed.
Purpose of the Study:
- To evaluate the safety, biodistribution, and internal radiation dosimetry of the novel PET tracer (18)F-ICMT-11.
- To assess the feasibility of using (18)F-ICMT-11 for noninvasive apoptosis imaging in humans.
Main Methods:
- Eight healthy volunteers received an intravenous bolus injection of (18)F-ICMT-11.
- Whole-body PET/CT scans were acquired at multiple time points up to 4 hours post-injection.
- Safety, biodistribution, and radiation dosimetry were assessed using quantitative imaging and sample analysis, with calculations performed using OLINDA/EXM 1.1.
Main Results:
- (18)F-ICMT-11 was well-tolerated with no serious adverse events reported.
- The mean effective dose was estimated at 0.025 ± 0.004 mSv/MBq, comparable to other (18)F PET tracers.
- The highest absorbed doses were to the gallbladder wall, small intestine, and upper large intestinal wall, with elimination via renal and hepatobiliary routes.
Conclusions:
- (18)F-ICMT-11 exhibits a favorable safety and dosimetry profile in healthy humans.
- The tracer is comparable to commonly used (18)F PET agents.
- These results support the further clinical development of (18)F-ICMT-11 for apoptosis imaging in cancer patients.
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