Development of [18f]icmt-11 for imaging caspase-3/7 activity during therapy-induced apoptosis

Abstract

Insufficient apoptosis is a recognised hallmark of cancer. A strategy to quantitatively measure apoptosis in vivo would be of immense value in both drug discovery and routine patient management. The first irreversible step in the apoptosis cascade is activation of the “executioner” caspase-3 enzyme to commence cleavage of key structural proteins. One strategy to measure caspase-3 activity is Positron Emission Tomography using isatin-5-sulfonamide radiotracers. One such radiotracer is [18F]ICMT-11, which has progressed to clinical application. This review summarises the design and development process for [18F]ICMT-11, suggesting potential avenues for further innovation.