title: Positron emission tomography imaging of drug-induced tumor apoptosis with a caspase-3/7 specific [18F]-labeled isatin sulfonamide.
abstract: Of the molecular biochemical alterations that occur during apoptosis, activation of caspases, notably caspase-3, is probably the most attractive for developing specific in vivo molecular imaging probes. We recently designed a library of isatin-5 sulfonamides and selected [18F]ICMT-11 for further evaluation on the basis of subnanomolar affinity for activated capsase-3, high metabolic stability, and facile radiolabeling. In this present study, we have demonstrated that [18F]ICMT-11 binds to a range of drug-induced apoptotic cancer cells in vitro and to 38C13 murine lymphoma xenografts in vivo by up to 2-fold at 24 h posttreatment compared to vehicle treatment. We further demonstrated that the increased signal intensity in tumors after drug treatment, detected by whole body in vivo microPET imaging, was associated with increased apoptosis. In summary, we have characterized [18F]ICMT-11 as a caspase-3/7 specific PET imaging radiotracer for the assessment of tumor apoptosis that could find utility in anticancer drug development and the monitoring of early responses to therapy.
authors.affiliation: Comprehensive Cancer Imaging Center, Department of Oncology, Imperial College London Faculty of Medicine, Hammersmith Hospital, Du Cane Road, London W120NN, United Kingdom.
authors.forename: Quang-Dé
authors.initials: QD
authors.lastname: Nguyen
authors.forename: Graham
authors.initials: G
authors.lastname: Smith
authors.forename: Matthias
authors.initials: M
authors.lastname: Glaser
authors.forename: Meg
authors.initials: M
authors.lastname: Perumal
authors.forename: Erik
authors.initials: E
authors.lastname: Arstad
authors.forename: Eric O
authors.initials: EO
authors.lastname: Aboagye
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism*; D053179:Caspase 7 / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry; D006801:Humans; D007510:Isatin / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005047:Etoposide; D007510:Isatin; D003520:Cyclophosphamide; D053148:Caspase 3; D053179:Caspase 7; D002945:Cisplatin