Program Information

History Symposium - Radionuclide Therapy: Dr. Saul Hertz to Present

F Fahey¹, B Greenspan², G Sgouros³*, (1) Boston Children's Hospital, Boston, MA, (2) Augusta University, Augusta, GA, (3) Johns Hopkins University, Baltimore, MD

Presentations

4:30 PM : Saul Hertz and the Birth of Radioiodine Therapy - F Fahey, Presenting Author
5:00 PM : Radionuclide Therapy: Past, Present and Future Promise - B Greenspan, Presenting Author
5:30 PM : Radioiodine Therapy of Throid Cancer - The Prototypical Example of a Dosimetry-based, Precision Medicine Approach to Cancer Treatment - G Sgouros, Presenting Author

WE-G-108-0 (Wednesday, August 2, 2017) 4:30 PM - 6:00 PM Room: 108

Saul Hertz and the Birth of Radioiodine Therapy - Frederic Fahey

In 1941, Saul Hertz MD treated the first patient for thyroid disease with radioactive iodine. Sentinel event marked the birth of not only radioiodine therapy but the entire field of targeted radionuclide therapy which is seeing a rebirth 75 years later. This presentation will follow the events in both physics and medicine that led up to Dr. Hertz asking the most important question “Can iodine be made radioactive?” These include the association of iodine with thyroid metabolism, the understanding of radioactivity in general and later the ability to produce artificial radioactivity. Lastly, the tracer principle will be discussed in the context of radionuclide therapy. The experiments necessary to demonstrate the potential for this new therapy will also be discussed. The academic and political challenges that faced Dr. Hertz as he pursued this research will also be discussed.

Learning Objectives:
1. Discuss 3 advances necessary for consideration of radioiodine therapy
2. Describe 2 aspects radionuclide production that had to be addressed to provide an appropriate radionuclide for the therapy
3. List three challenges faced by Dr. Hertz with regard to carry our this research

Radionuclide Therapy: Past, Present and Future Promise - Bennett S. Greenspan

Past: I-131 was the first radionuclide therapy agent, with use beginning in the 1940’s as described by Fred Fahey, and was also the first theranostic agent. It was and still is used successfully in treating hyperthyroidism and also differentiated (papillary and follicular) thyroid cancer. Differentiated thyroid cancers trap and organify iodide in the formation of thyroid hormone, similar to but less effective than normal thyroid tissue, and I-131 therapy can take advantage of these features. In therapy of both hyperthyroidism and thyroid cancer, dosimetry is important. For hyperthyroidism, the goal for years was 80 uCi/g (7,000 rad/g), more recently many experts advocate 120 – 140 uCi/g. For thyroid cancer, remnant ablation can be achieved by a dose of 30,000 rad (300 Gy). A number of other agents have been used, almost exclusively for malignancies. P-32 was used for myeloproliferative diseases and metastatic ovarian carcinoma, but fell out of favor due to development of secondary malignancies. In the 1980s, I-131 metaiodobenzylguanidine (MIBG) was introduced as a diagnostic and therapeutic agent for treatment of neuroendocrine tumors, and radiolabeled antibodies to solid tumors were introduced. Somatostatin receptor-targeted radionuclide therapy was introduced to treat various solid tumors. Several agents were used for bone pain palliation from metastatic disease, initially P-32, then Strontium-89 chloride and Samarium-153 EDTMP. Hepatocellular carcinoma (hepatoma) was treated with I-131 lipiodol. Two agents were introduced to treat non-Hodgkin lymphoma, although one has been discontinued due to under-utilization. One other benign indication for radionuclide therapy was radiation synovectomy.
Present: I-131 continues to be an important component of therapy for hyperthyroidism and papillary/follicular thyroid cancer. Somatostatin receptor-targeted therapy and I-131 MIBG are in current clinical use. Hepatic metastases and hepatomas (which is off-label) are now treated with Yttrium-90 (Y-90) radioembolization (Y-90 labeled glass beads or resin beads) by intra-arterial injection. Within the last 3 years, Radium-223 dichloride, an alpha-emitter, was introduced to treat bone metastases from castrate-resistant metastatic prostate cancer. Lutetium-177 (lu-177) dotatate is now in clinical trials for treatment of neuroendocrine tumors.

Future promise: I expect future developments will include specifically targeted RN therapy to provide precision therapy, with targeting of various enzymatic pathways and cell surface receptors. These therapies will also rely on calculation of dosimetry, probably including intralesional dosimetry. These therapies may include combinations of alpha and beta emitters to take advantage of different characteristics of path length and energy levels, which could provide more comprehensive therapy.

Learning Objectives:
1. Discuss the physiological basis and use of I-131 for treatment of hyperthyroidism and for papillary/follicular thyroid cancer.
2. Discuss the use of somatostatin receptor-targeted therapy for neuroendocrine tumors.
3. Discuss how beta and alpha emitters may be used, possibly in various combinations.

Radioiodine therapy of thyroid cancer - the prototypical example of a dosimetry-based, precision medicine approach to cancer treatment - George Sgouros

The systemic administration of radioiodine for the treatment of thyroid diseases constitutes one of the first uses of a radionuclide for therapy; it is the only one still in routine use. Based upon the clinical observation that fractionated administration of radioiodine over a prolonged time-period led to reduced treatment efficacy and eventual radio resistance in patient with metastatic thyroid cancer, an approach was developed that would allow treatment with the maximum tolerable administered activity. A tracer-level of radioiodine activity was administered to enable blood and whole-body measurements that could be used to calculate a therapeutic administration that was constrained based upon whole-body retention and blood dose limits. These limits were derived from early incidences of patient morbidity and mortality. In short, radioiodine treatment led to the first formal treatment planning scheme for radionuclide therapy that was based upon measurements from a tracer study and that also drew upon dose vs response experience in patients. The above-described formulation was developed in the late 1950’s and early 1960’s. A decade later a dosimetry formalism was developed by the Medical Internal Radiation Dose (MIRD) Committee to estimate absorbed doses for radiopharmaceuticals that were being developed for imaging. Building upon early work using radiolabeled antibodies for cancer therapy, radiopharmaceutical therapy using alpha-particle emitters has shown promise. The return to therapeutic use of radionuclides has also required a re-examination of the role of dosimetry in radionuclide therapy and a return to the concepts developed for radioiodine treatment of thyroid cancer.

Learning Objectives:
1. Understand the origins and methodology of dosimetry-based radioiodine therapy of thyroid cancer
2. Be able to explain the distinction between dosimetry for a non-deterministic (risk) end-point vs a deterministic (efficacy, toxicity) end-point
3. Explain the relevance of radiobiological models in dosimetry and response prediction
4. Explain the how dosimetry/treatment planning in radiopharmaceutical therapy fits into the precision medicine paradigm.

Handouts

No handouts have been uploaded for this submission.

127-38217-416554-131046.pdf (F Fahey)

127-38218-416554-126355.pdf (B Greenspan)

127-38219-416554-131042.pdf (G Sgouros)

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