PET/CT in cancer research: from preclinical to clinical applications

Abstract

The identification of genetic and biochemical mechanisms underlying tumor growth and progression along with the unraveling of human genoma provided a plethora of new targets for cancer detection, treatment and monitoring. Simultaneously, the extraordinary development of a number of imaging technologies, including hybrid systems, allowed the visualization of biochemical, molecular and physiological aberrations linked to underlying mutations in a given tumor. In vivo evaluation of complex biological processes such as proliferation, apoptosis, angiogenesis, metastasis, gene expression, receptor-ligand interactions, transport of substrates and metabolism of nutrients in human cancers is feasible using PET/CT and radiolabeled molecular probes. Some of these compounds are in preclinical phases of evaluation whereas others have been already applied in clinical settings. Here we provide prominent examples on how some biological processes and target expression can be visualized by PET/CT in animal tumor models and cancer patients for the noninvasive detection of well-known markers of tumor aggressiveness, invasiveness and resistance to treatment and for the evaluation of tumor response to therapy.

Review of functional/anatomical imaging in oncology

“…While, for the most part, it is not incorporated into DNA, the regulation of thymidine kinase-1 is closely related to cell proliferation status; cells in the G1 to S phases of the cell cycle demonstrate up to 20-fold higher rates of TK-1 activity compared to cells in G0 or the onset of G1. [77] FLT is useful because it reflects cellular proliferation as determined by proliferating cell nuclear antigen (PCNA) and Ki-67 score. A detailed description of the cellular retention of FLT via the purine salvage pathway is reviewed by Salskov et al[73]…”

“…As the prevailing dogma predicts highly proliferating cells to be more sensitive to the effects of cytotoxic therapies, determining which tumors are highly proliferative prior to therapy may help with the selection of therapy. [77]In some tumors, 18 F-FLT uptake has been shown to decrease even before physical changes in lesion size can be measured, and before a decrease in 18 F-FDG PET is seen. [77] This decrease was found to correlate with decreased malignant cellular proliferation.…”

“…[77]In some tumors, 18 F-FLT uptake has been shown to decrease even before physical changes in lesion size can be measured, and before a decrease in 18 F-FDG PET is seen. [77] This decrease was found to correlate with decreased malignant cellular proliferation. 18 F-FLT has also been evaluated across a wide range of primary tumors, including lung, breast, brain, colon, esophageal, and head and neck malignancies as well as lymphoma, melanoma, and sarcoma.…”

“…[73, 78] With the exception of one trial involving patients with rectal cancers, the decrease in 18 F-FLT activity after beginning chemotherapy regimens was predictive of tumor response. [77] As noted recently by Del Vecchio et al, the initial post-therapy FLT scan must be performed early in the regimen in order to reflect the true anti-proliferative effects of the treatment. [77] Due to its limited ability to stage tumors, especially compared with 18 F-FDG PET, 18 F-FLT has been suggested as an important adjunct, but not a stand-alone modality, for oncologic imaging.…”

Preparation and affinity identification of glutamic acid-urea small molecule analogs in prostate cancer

“…Radionuclide-labeled tracer or molecular probes targeting tumor cells effectively identify tumor lesions that are challenging to detect with traditional imaging methods, and PET/CT has become a powerful tool for the clinical diagnosis of tumors (22). At present, 11 C-choline and other cell metabolic substrates are used as PET/CT tracers, which have achieved a certain efficacy in the diagnosis of Pca (23,24).…”