Bridging the Gap Between Preclinical and Clinical Evaluation of Therapeutic Candidates

Session 3

Individualizing Cancer Therapies using PET Imaging

Richard L. Wahl, M.D.
Departments of Radiology and Oncology
Division of Nuclear Medicine
Johns Hopkins University School of Medicine
Baltimore, MD

PET/CT imaging using the radiotracer 18F-Fluoro-2-deoxy-D glucose (FDG) has been established as a clinically useful tool for imaging a wide range of cancers offering quantitative functional and anatomical information. In general, PET imaging is able to detect smaller cancers than detected with anatomic imaging, with greater specificity. It has been shown in a diverse array of neoplasms that effective therapies of a wide variety of types generally rather quickly reduce glucose metabolism in cancers, before tumor shrinkage occurs, and these reductions in glucose metabolism are quite predictive of the ultimate success of the treatments. The use of PET with FDG for the early assessment of treatment response includes a baseline PET scan with a follow up PET scan after 1 or 2 cycles of treatment. Rapid and large declines in tumor glycolysis early after treatment is initiated have been generally associated with a continued response to treatment and a superior progression free survival period than seen in patients who do not have rapid reductions or in whom glycolysis does not decline with treatment. The obvious advantage of imaging this approach is that there is a prompt and direct biological read out of cancer treatment efficacy in the individual tumor of an individual patient. Thus, host, therapeutic and tumor factors contribute to the PET signal observed. This “read out” of treatment effect appears to be rather robust and general predictor of the efficacy of treatment regimens in the diseases in which it has been studied, particularly lymphoma, esophageal and breast cancers. Thus, if this approach were widely adopted, effective treatments can be continued while ineffective treatments can be changed at earlier time points than currently is the case, “response adaptive therapy”. Dose de-intensification might also be possible. This approach using PET with FDG also is potentially applicable using other tracers, such as those for proliferation, protein or membrane synthesis, etc. This early readout of treatment efficacy is also of considerable interest in drug development and may help achieve more quick determinations of which candidate agents to continue development of and which to not pursue. Other PET approaches include “response predictive” therapies which may be able to predict before treatment the receptor status, hypoxic state, etc. for cancers before treatments are started and adjust the treatment appropriately. This lecture will briefly review the available data on monitoring cancer response with PET, response adaptive therapy with PET, and will also address briefly the potential for response predictive PET algorithms.

Up to Top