SUN-LB26 Radioligand Theranostics of Endocrine-Related Cancers; A New Revolutionary Approach

摘要

The successful clinical development of octreotide targeting somatostatin receptors (SSRs) revolutionized treatment of Neuro Endocrine Tumors (NETs)and pituitary adenomas. Recently, clinical applications of peptide bioconjugates including octreotide have taken a giant leap forward into a new diagnostic and therapeutic arena of additional endocrine-related cancers including prostate, breast, and small cell lung cancers. Molecularly targeted radionuclide therapy (RT) opens new horizons for otherwise resistant or widely dispersed malignancies and has far-reaching implications as a personalized therapeutic approach. Cancer-type specific, radiolabeled diagnostic imaging agents have been developed to select patients who then receive precise radioligand therapy targeting the identified cancer cells. This RT using alpha or beta radiation is cytotoxic to targeted cancer cells, while nearby healthy cells are unharmed—minimizing side effects and improving patient quality of life. Thus, theranostics represent a groundbreaking approach to bring radionuclide endocrine cancer therapy to patients via a multidisciplinary team consisting of endocrinologists, surgeons, oncologists and nuclear medicine physicians. In recognition of this exploding new field, the US FDA approved 68Ga-DOTATOC and -DOTATATE for use in PET/CT and 177Lu-DOTATATE for the treatment of SSR-positive NETs. Clinical trials with new theranostic compounds are ongoing for prostate cancer (PSMA), breast cancer (bombesin receptor), and small cell lung cancer (cytokine receptor CXCR4). Exciting future developments will undoubtedly involve development of radionuclide agents targeting additional cell surface receptors, enzymatic pathways, and clonal variations as well as combinations of alpha- and beta-emitters. Health care facilities worldwideare in the process of adding RT to their armamentarium for cancer patients; this requires a multidisciplinary team approach to optimize access to and delivery of care. To advance the science and enable translation of theranostics worldwide, the Gordon Research Conferences (GRC) organization [www.grc.org] has selected the authors to organize a 5-day inaugural meeting on Radionuclide Theranostics for the Management of Cancer in June 2020 [https://www.grc.org/radionuclide-theranostics-for-the-management-of-cancer-conference/2020/]that brings together cancer biologists, radiation physicists, receptor pharmacologists, nuclear medicine physicians, and industry representatives to 1) Identify new molecular targets and targeting vectors for specific malignancies; 2) Explore development of novel radionuclides and molecularly targeted radiopharmaceuticals; and 3) Optimize therapeutic benefits based on an understanding of radionuclide risks to normal tissues. This presentation will review the key topics discussed during this GRC meeting