Radioactive iodine (131I) therapy for differentiated thyroid cancer in Japan: current issues with historical review and future perspective.

Radioactive iodine (RAI, (131)I) has been used as a therapeutic agent for differentiated thyroid cancer (DTC) with over 50 years of history. Recently, it is now attracting attention in medical fields as one of the molecular targeting therapies, which is known as targeted radionuclide therapy. Radioactive iodine therapy (RIT) for DTC, however, is now at stake in Japan, because Japan is confronting several problems, including the recent occurrence of the Great East Japan Disaster (GEJD) in March 2011. RIT for DTC is strictly limited in Japan and requires hospitalization. Because of strict regulations, severe lack of medical facilities for RIT has become one of the most important medical problems, which results in prolonged waiting time for Japanese patients with DTC, including those with distant metastasis, who wish to receive RIT immediately. This situation is also due to various other factors, such as prolonged economic recession, super-aging society, and subsequent rapidly changing medical environment. In addition, due to the experience of atomic bombings in Hiroshima and Nagasaki, Japanese people have strong feeling of "radiophobia". There is fear that GEJD and related radiation contamination may worsen this feeling, which might be reflected in more severe regulation of RIT. To overcome these difficulties, it is essential to collect and disclose all information about the circumstances around this therapy in Japan. In this review, we would like to look at this therapy through several lenses, including historical, cultural, medical, and socio-economic points of view. We believe that clarifying the problems is sure to lead to the resolution of this complicated situation. We have also included several recommendations for future improvements.

Don Lawrence and the "k-capture" revolution.

PURPOSE: The practice of brachytherapy was in steep decline in the mid-20th century, largely because of safety issues. This article explores the innovations that revitalized brachytherapy with special attention to the introduction of low-energy seeds for permanent implantation. METHODS AND MATERIALS: Literature review; interviews; and the memos, records, and correspondence of Donald C. Lawrence. RESULTS: Paul Harper first proposed the use of radionuclides that decay by k-capture in the 1950s. But it was the vision and tenacity of health physicist Donald Lawrence that led to the successful implementation of I-125 (in the 1960s) and Cs-131 (40 years later).

From prophylaxis to atomic cocktail: circulation of radioiodine.

This paper is a history of iodine. To trace the trajectory of this element, goiter is used as a guideline for the articulation of a historical account, as a representation of thyroid disorders and of the spaces of knowledge and practices related to iodine. Iodine's journey from goiter treatment and prophylaxis in the late interwar period took on a new course after WWII by including the element's radioactive isotopes. I intend to show how the introduction of radioiodine contributed to stabilize the epistemic role of iodine, in both its non-radioactive and radioactive form, in thyroid gland studies and in the treatment of its disorders.

Measurement of bone mineral in vivo: an improved method

The mineral content of bone can be determined by measuring the absorption by bone of a monochromatic, low-energy photon beam which originates in a radioactive source (iodine-125 at 27.3 kev or americium-241 at 59.6 kev). The intensity of the beam transmitted by the bone is measured by counting with a scintillation detector. Since the photon source and detector are well collimated, errors resulting from scattered radiation are reduced. From measurements of the intensity of the transmitted beam, made at intervals across the bone, the total mineral content of the bone can be determined. The results are accurate and reproducible to within about 3 percent.

[Radioisotope department in Motol--the flow of time]. / Radioizotopové oddelení v Motole - jak sel cas.

The radioisotope department in Motol was established on the 1st of June 1957 as the part of The Research Institute of Endocrinology founded by Assoc. Prof. Karel Silink. In the beginning, the department included 20 beds and its main activity consisted of radioiodine treatment of hyperthyroidism. Since 1965 the attention has been paid to the treatment of thyroid cancer, and this tradition continues till this time. The article reviews the main directions of development of this department since the very beginning to present.

Radioactive iodine in thyroid medicine--how it started in Sweden and some of today's challenges.

In Sweden, radioactive iodine for thyroid diagnostics and therapy was introduced by Jan Waldenström (1906-1996) and Bengt Skanse (1918-1963). The paper describes the start of the clinical use of radioiodine, the various iodine isotopes available, measurement techniques and dosimetry. There are still problems to solve in relation to an optimal clinical use of radioiodine. One of the remaining challenges is to get consensus about the goal of the treatment of hyperthyreosis, as well as about a method for individual absorbed dose calculations. Careful dose estimates will prevent unnecessary radiation exposure and constitute a base for a future optimised radioiodine therapy. For the dose calculation, it is important to understand if there is any clinically significant temporary reduction in the ability of thyroid tissue to trap or retain 131I-iodide following prior administration of a diagnostic activity of 131I-iodide (stunning of the thyroid). This may be of special concern in connection with treatment of thyroid cancer and its metastases. Finally, the production capacity, availability and delivery of 123I have to be improved to increase clinical access to this radionuclide, which is optimal for diagnostic imaging and which gives lower absorbed dose and therefore also less risk for thyroid stunning than 131I.

Estimate of European 129I releases supported by 129I analysis in an Alpine ice core.

129I in the European environment originates predominantly from the industrial nuclear fuel reprocessing plants Sellafield (Great Britain), Marcoule, and La Hague (both France). While reliable data on 129I releases from La Hague exist for the whole period of operation, less is known about the contributions from Sellafield and Marcoule. For those periods where no data are available, i.e., for the first 16 years of the Sellafield operation and for the first 3 decades of the Marcoule operation, we estimated releases into the atmosphere of 118 GBq and 825 GBq, respectively. Hence, Marcoule was the major European source of airborne 129I, contributing about 45% to the total airborne 129I releases from all the European reprocessing facilities, until it was decommissioned in 1997. The estimated total emissions were compared with 129I deposition fluxes for the time period 1970-2002, obtained from the analysis of an ice core from Fiescherhorn glacier, Swiss Alps (46 degrees 33'N, 08 degrees 04'E; 3900 m asl). The temporal evolution of the 129I deposition agrees well with the total 129I releases into the atmosphere from the European reprocessing facilities and from atmospheric nuclear weapons tests, supporting our estimated release rates. However,the 129I concentrations and deposition fluxes at Fiescherhorn glacier were a factor of 6 lower than values obtained from the analysis of rainwater collected near Zurich (408 m asl) in Switzerland in the years 1994-97. This suggests a strong vertical concentration gradient of 129I, typical for water-soluble atmospheric trace species which are removed from the atmosphere in the course of days by precipitation scavenging, and must be taken into account if glaciers are used as an archive for a retrospective quantification of 129I deposition fluxes. In addition, the temporal evolution of the contribution of 129I re-emitted from the ocean's surface for the 129I inventory in the atmosphere was quantified for the first time. Although the annual amount of 129I released this way was very low until the early 1990s, it is similar to the airborne 129I releases from Sellafield and La Hague in the present time.

Monitoring iodine-129 in air and milk samples collected near the Hanford Site: an investigation of historical iodine monitoring data.

While other research has reported on the concentrations of (129)I in the environment surrounding active nuclear fuel reprocessing facilities, there is a shortage of information regarding how the concentrations change once facilities close. At the Hanford Site, the Plutonium-Uranium Extraction (PUREX) chemical separation plant was operating between 1983 and 1990, during which time (129)I concentrations in air and milk were measured. After the cessation of chemical processing, plant emissions decreased 2.5 orders of magnitude over an 8-year period. An evaluation of (129)I and (127)I concentration data in air and milk spanning the PUREX operation and post-closure period was conducted to compare the changes in environmental levels. Measured concentrations over the monitoring period were below the levels that could result in a potential annual human dose greater than 1 mSv. There was a measurable difference in the measured air concentrations of (129)I at different distances from the source, indicating a distinct Hanford fingerprint. Correlations between stack emissions of (129)I and concentrations in air and milk indicate that atmospheric emissions were the major source of (129)I measured in environmental samples. The measured concentrations during PUREX operations were similar to observations made around a fuel reprocessing plant in Germany. After the PUREX Plant stopped operating, (129)I concentration measurements made upwind of Hanford were similar to the results from Seville, Spain.

[The use of radioactive iodine in diagnosing thyroid diseases in Iceland. 1964]. / Notkun geislajods (I131) vid greiningu skjaldkirtilssjúkdóma á Islandi. Ad mestu eftir erindi sem flutt var í L.R. 13 nóvember 1963.

A brief description of human iodine metabolism is given. The results of 4 hours, 24 hours and 48 hours thyroid I-131 uptake and 48 hours PBI-131 measurements in 88 (28 males, 60 females) euthyroid volunteers are presented (Table I, fig. 2 and 3). The uptake in Icelandic euthyroids is ca. 50% lower than in euthyroids in Great Britain and U.S.A. (Table II). A 4 hours uptake > 21% of dose is the best criterion for hyperthyrodism, but a 48 hours uptake < 5% the best criterion for hypothyroidism. 48 hr PBI-131 is of no aid in diagnosis of hypothyroidism, but of some value in the diagnosis of hyperthyroidism (> 0.2% dose/1 plasma).Clinical assessment of 96 patients (10 hypothyr. 49 euthyroid. 37 hyperthyr.) is compared with the assessment based on I-131 studies (tabl. III & IV, fig. 4,5 and 7). The results of TSH stimulation test on 1 clin. Euthyroid with low uptake and 7 hypothyroids (6 primary, 1 secondary) are presented (fig. 6). BMR results (normal = 15%) in 56 of these patients are compared with clinical assessment (table V). No correlation between I-131 uptake and BMR was found in euor hypothyroid, but some correlation was found in hyperthyroids (r = + 0.53).

History of disorders of thyroid dysfunction.

The first description of thyroid diseases as they are known today was that of Graves disease by Caleb Parry in 1786, but the pathogenesis of thyroid disease was not discovered until 1882-86. Thyroidectomy for hyperthyroidism was first performed in 1880, and antithyroid drugs and radioiodine therapy were developed in the early 1940s. Thomas Curling first described hyopothyroidism (myxoedema) in 1850 and the cause and suitable treatment were established after 1883. This paper reviews the main landmarks in the history of thyroid disease, supplemented by a brief discussion of the historically relevant scientific aspects of the thyroid gland, and the evolution of endocrinology as a formal discipline.

Harold Knapp and the geography of normal controversy: radioiodine in the historical environment.

In 1962, after high levels of the isotope Iodine-131 were detected in Utah milk supplies, Dr. Harold Knapp, a mathematician working for the AEC's Division of Biology and Medicine, developed a new model of estimating, first, the relation between a single deposition of radioactive fallout on pasturage and the levels of Iodine-131 in fresh milk and, second, the total dose to human thyroids, resulting from daily intake of the contaminated milk. The implications of Knapp's findings were enormous. They suggested that short-living radioiodine, rather than long-living nuclides such as radiostrontium, posed the greatest hazard from nuclear test fallout and that children raised in Nevada and Utah during the 1950s had been exposed to internal radiation doses far in excess of recommended guidelines. This paper explores the explicit historical revisionism of Knapp's study, his refusal, contra normal AEC practices of knowledge production and spatial representation, to distance himself from the people and places downwind from the Nevada Test Site, and the reactions his work provoked among his AEC colleagues.

How the field of thyroid endocrinology developed in France after World War II.

This microhistory analyzes the transformation of French medical practice after World War II. Before the 1940s, coordinated clinical and experimental studies on a patient with thyroid disease were nonexistent. Starting in 1945, thyroid endocrinology was pushed forward by the use of radioiodine, which led pediatricians to rethink the hereditary transmission of thyroid diseases, stimulated by the school of biochemistry headed by Jean Roche, who participated in the elucidation of thyroid-hormone metabolism. Roche knew how to listen to hospital clinicians, who, in return, gave him free access to patients to conduct investigations on thyroid metabolism. Radioiodine proved to be sufficiently flexible to respond to the respective information needs of clinicians and biochemists, and was also responsible for the profound transformation of scientific reasoning: the chemical framework that had dominated thyroid studies since the discovery of thyroid iodine (1896) was replaced by the hormone paradigm.