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, (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.


CONCLUSIONS
(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.
Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
Amarnath
A
Challapalli
Laura M
LM
Kenny
William A
WA
Hallett
Kasia
K
Kozlowski
Giampaolo
G
Tomasi
Mihir
M
Gudi
Adil
A
Al-Nahhas
R Charles
RC
Coombes
Eric O
EO
Aboagye
D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D001386:Azides / Q000009:adverse effects / Q000493:pharmacokinetics*; D053148:Caspase 3 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods*; D011829:Radiation Dosage; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
C571272:(18)F-ICMT11; D001386:Azides; D007211:Indoles; D019275:Radiopharmaceuticals; D053148:Caspase 3
18F-ICMT-11; apoptosis; biodistribution; caspase-3; dosimetry