Abstract B61: Paving the way to Personalized Medicine: Diagnosis, prevention and treatment of early stage bone metastatic disease in prostate cancer patients with Theragnostic Radiopharmaceuticals.

A major advantage of radionuclides is that they emit radiation of different radiobiological effectiveness and range of action. This presentation will introduce a relatively novel paradigm that involves specific individual radionuclides or radionuclide pairs that have emissions that allow pre-therapy low-dose imaging plus higher-dose therapy in the same patient. We have made an attempt to sort out and organize a number of such theragnostic radionuclides and radionuclide pairs that may potentially bring us closer to the age-long dream of personalized medicine for performing tailored low-dose molecular imaging (SPECT/CT or PET/CT) to provide the necessary pre-therapy information on biodistribution, dosimetry, the dose limiting critical organ or tissue, and the maximum tolerated dose (MTD), etc. If the imaging results then warrant it, it would be possible to perform dose ranging studies and higher-dose targeted molecular therapy in in the same patient with the same radiopharmaceutical. Tin-117m (T1/2 14.0 d; γ 159 keV, 86%) is an ideal radionuclide for the development of theragnostic radiopharmaceuticals. In contrast to most other therapeutic beta emitters, Sn-117m decays via isomeric transition with the emission of monoenergetic conversion electrons (127, 129, and 152 keV; abundance 65, 12, and 26% respectively). These emissions have short discrete ranges of between 0.22 and 0.29 mm in tissue and they deposit an intense radiation dose only within this short range in the the selectively targeted area and causing much reduced dose to radiation sensitive bone marrow and other normal organs. Moreover, its 159 keV γ-photon is perfect for pre-therapy imaging in the same patient. We have shown Sn-117m to be effective for therapy of cancer and other inflammatory conditions (e.g., atherosclerotic disease). The results of the Phase II clinical trial of tin-117m DTPA for metastaic bone pain palliation (using reactor-produced tin-117m, with specific activity ranging between 8-20 Ci/g of tin) will be presented. NCA (no-carrier-added) tin-117m is also being developed and tested for the prevention/therapy of early stage bone metastases in prostate cancer patients and for use in radioimmunotherapy. A phase II/III clinical trial for the imaging and treatment of bone metastases in prostate cancer patients is in the planning stage for 2013. A brief description of the recently developed new or modified methods at BNL for the production and radiochemistry of a number of other potential theragnostic radionuclides, whose nuclear, physical, and chemical characteristics seem to show great promise for personalized cancer therapy will be provided. Work at BNL supported by the U.S. Department of Energy under Contract # DE-AC02-98CH10886. Citation Format: Suresh C. Srivastava. Paving the way to personalized medicine: Diagnosis, prevention, and treatment of early-stage bone metastatic disease in prostate cancer patients with theranostic radiopharmaceuticals. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B61. Note: This abstract was not presented at the conference.