Radiopharmaceutical therapy in the era of precision medicine

Abstract

Precision medicine is the selection of a treatment modality that is specifically tailored to the genetic and phenotypic characteristics of a particular patient's disease. In cancer, the objective is to treat with agents that inhibit cell signalling pathways that drive uncontrolled proliferation and dissemination of the disease. To overcome the eventual resistance to pathway inhibition therapy, this treatment modality has been combined with chemotherapy. We propose that pathway inhibition therapy is more rationally combined with radiopharmaceutical therapy (RPT), a cytotoxic treatment that is also targeted. RPT exploits pharmaceuticals that either bind specifically to tumours or accumulate by a broad array of physiological mechanisms indigenous to the neoplastic cells to deliver radiation specifically to these cells. Consistent with pathway inhibition therapy and in contrast to chemotherapy, RPT is well tolerated. However, the potential of RPT has not been fully exploited; for the most part, treatment has been implemented without using the ability to customise RPT by imaging and deriving individual patient tumour and normal organ radiation absorbed doses. These are more closely related to biological response and their determination should enable RPT treatment administration to maximum therapeutic benefit by treating to normal organ tolerance or demonstrating futility via tumour dosimetry. This is the essence of precision medicine.

Keywords: Dosimetry; Patient-specific radionuclide therapy; Radiopharmaceutical therapy; Treatment planning.