Imaging apoptosis with positron emission tomography: 'bench to bedside' development of the caspase-3/7 specific radiotracer [(18)F]ICMT-11.
The capacity to evade apoptosis has been defined as one of the hallmarks of cancer and, thus, effective anti-cancer therapy often induces apoptosis. A biomarker for imaging apoptosis could assist in monitoring the efficacy of a wide range of current and future therapeutics. Despite the potential, there are limited clinical examples of the use of positron emission tomography for imaging of apoptosis. [(18)F]ICMT-11 is a novel reagent designed to non-invasively image caspase-3 activation and, hence, drug-induced apoptosis. Radiochemistry development of [(18)F]ICMT-11 has been undertaken to improve specific radioactivity, reduce content of stable impurities, reduce synthesis time and enable automation for manufacture of multi-patient dose. Due to the promising mechanistic and safety profile of [(18)F]ICMT-11, the radiotracer is transitioning to clinical development and has been selected as a candidate radiotracer by the QuIC-ConCePT consortium for further evaluation in preclinical models and humans. A successful outcome will allow use of the radiotracer as qualified method for evaluating the pharmaceutical industry's next generation therapeutics.
Department of Surgery and Cancer, Imperial College, London, UK.
Quang-Dé
QD
Nguyen
Amarnath
A
Challapalli
Graham
G
Smith
Robin
R
Fortt
Eric O
EO
Aboagye
D017209:Apoptosis / Q000502:physiology; D001386:Azides / Q000737:chemistry / Q000493:pharmacokinetics; D053148:Caspase 3 / Q000032:analysis / Q000378:metabolism; D053179:Caspase 7 / Q000032:analysis / Q000378:metabolism; D003952:Diagnostic Imaging / Q000379:methods*; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000493:pharmacokinetics; D007510:Isatin / Q000031:analogs & derivatives / Q000737:chemistry; D008954:Models, Biological; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000628:therapy; D019095:Point-of-Care Systems; D049268:Positron-Emission Tomography / Q000379:methods; D011849:Radioactive Tracers; D013379:Substrate Specificity; D013449:Sulfonamides / Q000737:chemistry / Q000493:pharmacokinetics; D057170:Translational Research, Biomedical / Q000379:methods
C571272:(18)F-ICMT11; D001386:Azides; D005462:Fluorine Radioisotopes; D007211:Indoles; D011849:Radioactive Tracers; D013449:Sulfonamides; D007510:Isatin; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7