The LuGenIum Triptych: Ode to a Theranostic Transcriptome

Abstract

AbstractIt all began in Weimar, at the Goethe National Museum in Weimar, a magnificent and placid place, redolent in history and culture, where Prof. Richard Baum organized the fourth Mitteldeutsches Neuroendokriner Tumor Symposium, in June 2013 (Fig. 7.1). Richard has always been a pioneer and the first to understand and disseminate the importance of many innovations, including the now popular theranostic concept. Unlike many conservative and “predictable” scientific gatherings, his meetings have always been avant-garde and pivotal in defining the trends for the future. To my delight and pleasure, I was invited to participate in what I knew would be a tour de force of the trailblazers of innovative nuclear medicine. Inspired by such greatness, we subsequently established the LuGenIum Consortium for Independent Research to addressed some of the major challenges in the use of peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NETs), which are the prediction of efficacy and toxicity and the consequent patient stratification. In the following years, we conducted clinical trials to understand the role of individual predisposition and specific tumor genomic profile in the response and toxicity to PRRT. Our specific aims were to, first, conduct a retrospective analysis of toxicity to PRRT (i.e., define the problem) in a large patient cohort, then to conduct two prospective studies (assess the efficacy of the ideas). To this aim, we firstly identified NETs at a genomic level and assessed the response to PRRT with a PCR-based blood analysis, and, secondly, we analyzed markers of long-term toxicity in patients previously undergone to PRRT, with a PCR-based blood analysis. During our investigations, we identified a new biomarker, the PRRT predictive quotient, or PPQ, which demonstrated 95% accuracy in predicting the response to PRRT in the three prospective series that were studied under the LuGenIum umbrella. These results provide the demonstration that PPQ is a predictive biomarker and a measure of radiosensitivity. We also demonstrated in these patients that the NET identifying circulating transcriptomic signature NETest was able to accurately monitor the course of PRRT during its delivery, as opposed to imaging, which becomes reliable only after treatment completion. The results of these studies opened a new era for treatment individualization and optimization.