Novel radiopharmaceuticals for therapy

In the era of personalized medicine, "targeted radionuclide therapy" (TRT) is designed to damage only the cancerous cells while sparing unnecessary damage to the adjacent healthy cells/tissues. Unlike conventional external beam radiation therapy, TRT is intended to cause less or no collateral damage to normal tissues, as it aims at achieving targeted drug delivery either to a clinically diagnosed cancer not amenable to surgery or to metastatic tumor cells and tumor cell clusters, thus providing systemic therapy of cancer. Currently there are hundreds of new pathway-targeted anticancer agents undergoing phase II and phase III clinical trials. TRT is just one type within the domain of "targeted therapies. " In addition to the effective targeted radiopharmaceuticals already well validated for routine clinical use, newer radiolabeled agents are still in the phase of either preclinical or clinical validation. This chapter describes the main physical and radiochemical characteristics of radionuclides that have potential or have already been employed to label biologically reactive molecules for the development of novel radiopharmaceuticals for therapy. Some of these agents have entered advanced clinical trials in tumor-bearing patients. Results of these clinical trials cover a wide spectrum of potential clinical usefulness. The chapter is divided into two main parts depending on the type of particle emission (α or β- associated or not with the emission of either γ-rays or β+ particles). Within each domain, there is some exchange of experience and shift of focus in the various phases of development, depending on the modalities of ascertaining efficient tumor targeting according to the principles of theranostics. Theranostics is often performed utilizing the same molecule labeled with two different radionuclides, one radionuclide for imaging and another for therapy, in order to achieve a personalized treatment approach to the patient. Nowadays, the fields of interest include the well-established use of radioactive iodine in differentiated thyroid cancer, radiolabeled metaiodobenzylguanidine (MIBG) in neuroblastoma, and the clinical impact of peptide receptor radionuclide therapy (PRRT) in the management of neuroendocrine tumors. Furthermore, the more cutting-edge and recently introduced theranostic approaches will be reviewed, such as the radioligand therapy with 177Lu-PSMA-ligand and targeted alpha therapy in castration-resistant prostate cancer.