Radiopharmacology and molecular imaging of PD-L1 expression in cancer

Abstract

Introduction

Immunotherapy [(specifically, antibodies blocking programmed death ligand-1 (PD-L1)] is a valuable option in cancer treatment because it leads to durable tumour regression and improves survival in several cancers. Patients with PD-L1 expressing tumours benefit from this therapy, but currently it can only be determined through biopsy, which may be inconclusive or impossible due to lesion location, associated risks, intratumoral and interlesional heterogeneity. Therefore, radio-immune-imaging with a specific radiopharmaceutical is ideally placed to play an important role when performing real-time, in vivo, whole-body and non-invasive PD-L1 expression mapping.

Purpose

To describe and summarise published scientific data on imaging PD-L1 expression using radiopharmaceuticals and discuss future directions in this research field.

Methods

A summary review of the literature was done through PubMed to search papers that described and included radiopharmaceuticals to image PD-L1 expression. Only English papers published until April 2018 that detailed laboratorial and animal procedures were selected.

Results

Eleven pre-clinical papers published between 2015 and 2018 were included. Four studies used anti-PD-L1 radiopharmaceuticals labelled with Indium-111, 4 with Copper-64, 2 with Fluoride-18 and 1 with both Copper-64 and Gallium-68. All of them had identical protocols and showed similar radiopharmaceutical biodistribution. They reported successful anti-PD-L1 labelling, with high tumour–background ratio (mainly when spleen uptake was saturated with unlabelled/cold antibody).

Conclusions

All reported radiopharmaceuticals had high sensitivity and specificity to identify tumours with PD-L1 expression in animal model. Clinical experiments appear to be now justifiable.