A Review of the History of Radioactive Iodine Theranostics: The Origin of Nuclear Ontology.

Studies on the first years of radioactive iodine (RAI) use in thyroid diseases have focused on hyperthyroidism. Saul Hertz's success with RAI in thyrotoxicosis fueled a seamless transition to Samuel Seidlin's investigations with RAI in thyroid cancer. These landmark events embody nuclear ontology, a philosophical foundation for the creation and existence of radio-therapeutic principles that continue to influence clinical practices today. Laying this ontological foundation, Dr. Saul Hertz who is the founding director of Massachusetts General Hospital Thyroid Clinic, affiliated with Harvard University created a framework for RAI theranostics with preclinical experiments and clinical cases from 1937 to 1942. The first thyroid cancer treatment with RAI was applied in 1942 by Samuel Seidlin. The sensational effect of the first application was interestingly powerful enough to overshadow scientific data. Seidlin and colleagues assembled a sixteen-patient series showcasing a unique entity: functional thyroid metastases that respond to RAI. Other investigations at the time demonstrated that RAI had little efficacy as a therapeutic agent, mainly because most thyroid tumors do not form colloid, and therefore cannot concentrate RAI. These findings were soon overshadowed by a mainstream article in the October 1949 issue of Life that portrayed RAI as a lifesaving therapy for thyroid cancer. The paradigm was set, and later writings by William H. Beierwaltes and other prominent nuclear medicine physicians established the primary goals and principles of RAI therapy. The developments in theoretical physics and nuclear instrumentation and the scientists who made these developments in the early years contributed greatly to the development of the concept. In the field of nuclear medicine, William H. Beierwaltes has gone down in our history as a clinical researcher with his most important contributions. The classical paradigm that started with him has carried us to today's molecular theranoistic viewpoint. This paper examines controversial topics in the advent of thyroid theranostics, and applies historical significance to current discussions on the role of RAI in thyroid cancer management. Another paradigm shift is on the horizon as thyroidology enters the age of genomics. The molecular theranostic profiles will soon be incorporated into a dynamic clinical decision-making and management algorithm for thyroid surgery and RAI therapy. From now on, nuclear oncology will gain a new ontological identity with molecular pathology and new theranostic expansions.