Novel oncologic PET tracer captures cell death

A new facet of cancer imaging targets apoptosis, the process of cell death, to help select and monitor anticancer therapies, according to a study published Aug. 15 in the Journal of Nuclear Medicine.

Amarnath Challapalli, MD, a research fellow in the department of surgery and cancer at Imperial College London in London, United Kingdom, and colleagues tested the biodistribution, dosimetry and safety of an emerging fluorine-based imaging agent, F-18 ICMT-11, short for 18F-(S)-1-((1-(2-fluoroethyl)-1H-[1,2,3]-triazol-4-yl)methyl)-5-(2(2,4-difluorophenoxymethyl)-pyrrolidine-1-sulfonyl)isatin. This tracer seeks out the “executioner” caspase-3, an enzyme essential to the apoptosis signaling pathway controlling the demolition of cell structures. Apoptosis results from a range of radiation-based and pharmacologic mechanisms, but the process of cell death is largely the same and involves caspases.

“Moreover, one of the most noticeable and specific features of apoptosis is the degradation of the DNA into numerous fragments, often down to multiples of 200 base pairs, driven by the activation of caspase-3, the central effector caspase, which makes it an attractive biomarker of apoptosis,” wrote Challapalli et al.

For this first-ever human study, eight healthy subjects underwent whole body PET/CT imaging with F-18 ICMT-11 at six points of time and up to four hours after injection. Quantitative analyses were conducted for all scans and patients’ blood, plasma and urine were analyzed for radioactivity and radiotracer viability. Results showed that F-18 ICMT-11 was safe and effective with no major adverse effects.

The tracer demonstrated rapid vascular washout and renal as well as liver elimination. Renal excretion was found to be comparably lower at 18 percent in four hours and gallbladder localization higher than other F-18 based tracers such as FDG. A possible impact of this tracer’s development is the ability to gauge response to therapy earlier, making it especially useful for research.

“Effective anticancer therapy often requires induction of tumor cell death through apoptosis,” wrote the authors. “Monitoring of this process could provide important predictive outcome information in the context of routine patient management and early clinical trials. The apoptotic index has been shown to correlate with chemotherapy efficacy and to be of prognostic significance. A noninvasive apoptosis imaging technology such as PET could permit the detection of biologic changes in the tumor that evolve over hours of initiating treatment. This shorter time frame is in contrast to changes in tumor size that evolve over months, which forms the basis for Response Evaluation Criteria in Solid Tumors guidelines.”

Further clinical trials and regulatory approval are needed before F-18 ICMT-11 could be used in the clinic to predict the effectiveness of and monitor response to cancer treatments.