Non-conventional and Investigational PET Radiotracers for Breast Cancer: A Systematic Review

Abstract

Breast cancer is one of the most common malignancies in women, with high morbidity and mortality rates. In breast cancer, the use of novel radiopharmaceuticals in nuclear medicine can improve the accuracy of diagnosis and staging, refine surveillance strategies and accuracy in choosing personalized treatment approaches, including radioligand therapy. Nuclear medicine thus shows great promise for improving the quality of life of breast cancer patients by allowing non-invasive assessment of the diverse and complex biological processes underlying the development of breast cancer and its evolution under therapy. This review aims to describe molecular probes currently in clinical use as well as those under investigation holding great promise for personalized medicine and precision oncology in breast cancer.

The Role of Molecular Imaging in Personalized Medicine

“…The most often used glucose analog is 18F-fluorodeoxyglucose (FDG). Some novel receptor-active peptides have found usage in the transport and phosphorylation of FDG, but then the FDG is stuck [ 2 , 4 , 10 , 12 , 14 , 17 , 20 , 21 , 23 , 47 , 49 , 53 , 56 , 60 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 ].…”

“…Molecular imaging is used widely in screening, detection and diagnosis, treatment, assessing disease heterogeneity and progression planning, molecular characteristics, and long-term follow-up. Moreover, it is able to detect very tiny tumors and assess their activity numerically, which makes molecular imaging one of the most scientific reasons that contributes greatly to expanding and developing the personalized medicine, research, clinical trials, and medical practice of cancer fields, evolving a new generation of platforms with greater accuracy and sensitivity for in vivo quantification and characterization of various biological processes [ 4 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ].…”

Molecular imaging as biomarker for treatment response and outcome in breast cancer

“…In addition to [ 18 F]FDG, [ 18 F]FES and HER2 visualizing tracers, other tracers visualizing other characteristics of breast cancer have been investigated to some extent in clinical trials. 11 , 103 …”

Adaptation to Hypoxia May Promote Therapeutic Resistance to Androgen Receptor Inhibition in Triple-Negative Breast Cancer

“…To facilitate the individualized treatment of tumors with anti-angiogenics, agents and probes that allow direct, non-invasive, and dynamic in vivo visualization of hypoxic regions of breast tumors, can inform clinical decision making by providing real-time information regarding the hypoxia status of the tumor, the extent of the re-normalization of the vessel architecture, as well as the changes in the interstitial delivery of therapeutics [ 146 ]. A 2016 study provided proof of principle that 18F-fluoromisonidazole-PET ([18F]-FMISO-PET) binds specifically to hypoxic regions and serves as a read-out for hypoxia reversion and is a tracer for visualizing both the re-normalization of tumor vasculature and vessel functionality, as well as the changes in the delivery of chemotherapeutics to different patient-derived xenografts [ 147 ].…”

“…The concomitant use of biomarkers such as [18F]-FMISO-PET or [18F]F-FAZA may galvanize the clinical implementation of combination regimens involving anti-AR treatments as well as anti-angiogenics/anti-hypoxia therapeutics because they enable a more optimal choice and dynamic monitoring of personalized treatments, as well as response assessment during therapy; indeed, such a strategic combination of diagnostics with therapeutics—termed theragnostics—embraces a level of precision oncology that pursues nimble shifts in therapy tailored based on changes in the molecular characteristics of tumors. Thus, the precise identification and quantitation of hypoxic levels via hypoxia-specific in vivo imaging techniques, such as PET and Single Photon Emission Computed Tomography (SPECT), will be critical to successfully designing optimal therapeutic strategies to co-target hypoxia along with AR in each individual TNBC patient [ 39 , 146 , 149 ].…”