Molecular imaging to guide systemic cancer therapy: Illustrative examples of PET imaging cancer biomarkers

Abstract

Molecular imaging agents have the ability to non-invasively visualize, characterize, and quantify the molecular biology of disease. Recent advances in nuclear probe development, particularly in PET radiotracers, have generated many new imaging agents with precise molecular targets. With such specificity, PET probes may be utilized as biomarkers to objectively interrogate and evaluate pathology. Whereas the current indications for PET imaging are predominately confined to staging and restaging of malignancy, the utility of PET greatly expands when utilized as a biomarker, the topic of this review. As an imaging biomarker, PET may be used to (1) measure target expression to select subsets of patients who would most benefit from targeted therapy; (2) measure early treatment response to predict therapeutic efficacy; and (3) relate tumor response to survival. This review will discuss the application of radiotracers to targeted cancer therapy. Particular attention is given to new radiotracers evaluated in recently completed clinical trials and those with current or potential clinical utility. The diverse roles of PET in clinical trails for drug development are also examined.

Keywords: Cancer biomarkers; Clinical trials; Positron emission tomography.

Fig. 1

FES-PET used to predict response to hormonal therapy in metastatic breast cancer patients. Pretreatment FES-PET (FES; left) and FDG-PET (FDG; middle) scans and follow-up FDG-PET post-therapy (FDG; right) scan are shown. Bone metastasis with robust FES and FDG uptake (A; top) demonstrates response at 3 months. Bone metastasis (solid arrow) without FES uptake, but with FDG uptake (B; bottom), demonstrates progressive disease at 6 months. Dashed arrows show normal liver FES uptake. Rx, treatment. FDG images are displayed on a consistent SUV scale for each patient pre- and post-therapy. FES is displayed on a scale of 0–5. (Originally published by the American Society of Clinical Oncology [33]).

Fig. 2

Early assessment of treatment response by FLT-PET. Fused FLT-PET/CT axial (upper) and coronal (lower) images demonstrate increased FLT uptake in an upper outer quarter breast tumor and axillary lymph node before therapy (left). After one cycle of neoadjuvant chemotherapy, there is substantial reduction in the primary breast tumor FLT uptake (middle) and resolution of FLT uptake after completion of neoadjuvant chemotherapy (right). Patient had pathologic complete response confirmed at surgery. Arrows refer to primary tumor site. This research was originally published in JNM, Ref . © by the Society of Nuclear Medicine and Molecular Imaging, Inc.).

Fig. 3

Complete metabolic response to chemotherapy in a patient with Hodgkin lymphoma. Pre-treatment fused FDG-PET/CT and FDG-PET images (A) show intense uptake in a large mediastinal mass and axillary lymphadenopathy. Post-treatment scan (B) shows a residual mediastinal mass, but without increased FDG uptake. Per the Lugano Classification, this represents a complete metabolic response and is considered a complete remission. FDG-uptake scale (SUV) is the same for both pre- and post-therapy images and is displayed on the right.