Gordon Lecture: Radiopharmaceutical Therapy: History, Current Status and Future Potential


Bennett S. Greenspan, M.D., M.S. received his M.D. degree from the University of Illinois in Chicago. He completed residencies in Diagnostic Radiology and Nuclear Medicine and is certified in Diagnostic Radiology and Nuclear Radiology by the ABR and in Nuclear Medicine by the ABNM. He received the M.S. degree in medical physics from UCLA. Dr. Greenspan is devoted to teaching of clinical nuclear medicine and also physics and radiation safety of nuclear medicine to nuclear medicine and radiology residents.  He is also keenly interested in quality and safety in Nuclear Medicine.
Below is a summary of his presentation

History - Radiopharmaceutical therapy began in 1941 with the efforts and insight of Saul Hertz, MD of MGH and also Arthur Roberts, PhD of MIT. From that beginning, I-131 has become an important agent for the treatment of benign and malignant thyroid disease. In the 1980s, two agents, Sr-89 chloride and Sm-153 EDTMP, were introduced for bone pain palliation. Somatostatin receptor targeted therapies were developed in the 1980s and 1990s, leading to FDA-approval of Lu-177 Dotatate in 2018. Radiolabeled antibodies were also being developed in the 1970s – 2000s, with the introduction of two agents in 2002 and 2003. Radium-223 dichloride was approved by the FDA in 2013 for treatment of castrate-resistant metastatic prostate cancer.

Current Status – I-131 is used in hyperthyroidism and in differentiated thyroid cancer. Peptide Receptor Radionuclide Therapy (PRRT) is used to treat neuroendocrine tumors, and Lu-177 Dotatate is the most recently approved agent. I-131 iobenguane was approved in 2018 for treatment of pheochromocytoma and paraganglioma. Hepatic metastases and hepatocellular carcinoma can be treated with Y-90 microspheres. Sm-153 EDTMP and Sr-89 chloride are available for bone pain palliation but are rarely used. Ra-223 dichloride is now in routine clinical use for treatment of bone metastases of metastatic prostate cancer.

Future Potential -  Industry predicts that 30% of NM procedures in 2030 will be radiopharmaceutical therapies, substantially increased from 13% currently. Lu-177 PSMA is being used in Germany and Australia, and it is expected to be approved in the US in the near future. We may also see approval of Ac-225 PSMA for prostate cancer, which is in use in Germany. I expect that in the near future radiopharmaceutical therapies will be specifically targeted. According to Dr. Richard Baum, cancers will be classified by molecular phenotypes first, and organ site secondarily. We will be able to take advantage of physical properties of various radionuclides (including path lengths, energy levels and half-lives), and will target various enzymatic pathways, cell-surface receptors, and clonal variations of metastases to provide precise targeting of malignant disease. The results of these advances, probably combined with other therapies, will result in better outcomes for patients with less morbidity. 

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