Theranostic Radiopeptides in Nuclear Oncology: Design, Preclinical Screening, and Clinical Translation

Abstract

AbstractCancer theranostics is an emerging and exciting field in nuclear medicine, whereby suitably designed radionuclide carriers, after injection to patients, seek and specifically interact with biomolecular targets overexpressed on cancer cells. When a diagnostic radionuclide is applied, molecular imaging with SPECT (gamma emitter) or PET (positron emitter) will reveal tumor lesions, allowing for initial diagnosis and assessment of disease spread and progression. Hence, molecular imaging represents a reliable tool for patient stratification, dosimetry and planning of therapy that follows next with the respective therapeutic radionuclide (beta, Auger electron, or alpha emitter) carrier in an integrated patient-tailored approach. In this way, patients are spared from ineffective and toxic therapies that only impair quality of life without any tangible benefit. Several recent examples have demonstrated the feasibility and efficacy of this strategy. Thus, the advent of radiolabeled somatostatin analogs in the management of neuroendocrine tumors on one hand, and the successful application of prostate-specific membrane antigen inhibitors to diagnose and combat prostate cancer on the other, are two elegant paradigms of this approach.In this chapter, we shall discuss important issues pertaining to the design and preclinical evaluation of peptide-based radioligands, focusing on compound examples developed in our center. The steps to be followed for clinical translation of selected analogs will be also briefly described. Emphasis will be given on the significance of pilot proof-of-principle studies in a small number of patients to guide further efforts toward drug development and registration.