The Use of Novel PET Tracers to Image Breast Cancer Biologic Processes Such as Proliferation, DNA Damage and Repair, and Angiogenesis

Abstract

The balance between proliferation and cell death is pivotal to breast tumor growth. Because of a combination of environmental and genetic factors leading to activation of oncogenes or inactivation of tumor suppressor genes, these processes become deregulated in cancer. PET imaging of proliferation, angiogenesis, and DNA damage and repair offers the opportunity to monitor therapeutic efficacy to detect changes in tumor biology that may precede physical size reduction and simultaneously allows the study of intratumoral and intertumoral heterogeneity.This review examines recent developments in breast cancer imaging using novel probes. The probes discussed here are not licensed for routine use and are at various stages of development ranging from preclinical development (e.g., the DNA repair marker γH2AX) to clinical validation in larger studies (such as the proliferation probe 3′-deoxy-3′-18 F-fluorothymidine [ 18 F-FLT]). In breast cancer, most studies have focused on proliferation imaging mainly based on 18 F-labeled thymidine analogs. Initial studies have been promising; however, the results of larger validation studies are necessary before being incorporated into routine clinical use. Although there are distinct advantages in using process-specific probes, properties such as metabolism need careful consideration, because high background uptake in the liver due to glucuronidation in the case of 18 F-FLT may limit utility for imaging of liver metastases.Targeting angiogenesis has had some success in tumors such as renal cell carcinoma; however, angiogenesis inhibitors have not been particularly successful in the clinical treatment of breast cancer. This could be potentially attributed to patient selection due to the lack of validated predictive and responsive biomarkers; the quest for a successful noninvasive biomarker for angiogenesis could solve this challenge. Finally, we look at cell death including apoptosis and DNA damage and repair probes, the most well-studied example being 18 F-annexin V; more recently, probes that target caspase endoproteases have been developed and are undergoing early clinical validation studies.Further clinical studies including analysis of test-retest variability are essential to determine sensitivity and future utility of these probes in breast cancer.

The impact of transcription on metabolism in prostate and breast cancers

“…11 C-sarcosine is also gaining interest as a radiotracer for PCa imaging as sarcosine, a metabolic product of choline is associated with PCa aggressiveness and progression (Piert et al 2017). In BCa, most studies have focused on 18 F-labelled thymidine analogues to assess cell proliferation, although promising results from using 11 C-choline have been reported in BCa patients (Kenny 2016).…”

Positron emission tomography in breast cancer: 18F- FDG and other radiopharmaceuticals

“…1-(29-deoxy-29-fluoro-b-D-arabinofuranosyl) thymine (FMAU) is another thymidine analog that has been developed for use in PET studies. Novel 18 F-benzamide analogs are also being developed as proliferation probes (Kenny, 2016). However, further clinical studies, recruiting larger groups of population, are needed in order to evaluate the preliminary results of these studies.…”

Molecular Imaging and Precision Medicine in Breast Cancer

“…L-methyl-11 C-methionine ( 11 C-MET) is an amino acid used in PET, and a small number of cases were found to have decreased 11 C-MET uptake after treatment with endocrine therapy or chemotherapy (71)(72)(73). Numerous others have a potential important role in the development and optimization of targeted therapies (7,54).…”