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At least 19 recordsLinked to original sources

The prediction of the relative toxicities of radium 224 and of radium 226 in the bones of mice using Monte Carlo techniques.

Toxicity studies using rodents have shown that the long-lived radium isotope radium 226 is about six times less toxic per unit of absorbed radiation dose to the skeleton than the short-lived isotope radium 224 with respect to the production of osteosarcoma. This difference in toxicity has been attributed to differences in the distribution of these isotopes. It has been suggested that 224Ra is more toxic than 226Ra because it decays on bone surfaces rather than within the volume of the bone mineral. However, in rodents many bone structures are small compared with the track length of the alpha particles and this explanation may be inadequate to explain the magnitude of the observed effect. Consequently, Monte Carlo calculations have been made to test the validity of the distribution-difference hypothesis. The results indicate that, for bone structures the size of those in mice, less than half of the observed difference in toxicity can be explained by considerations of the distribution of these radionuclides with respect to bone surfaces. Instead, it is suggested that the greater irradiation of trabecular than of cortical bone that is a characteristic of 224Ra is responsible for its enhanced toxicity.

Animals

A prospective trail comparing hysterectomy, hysterectomy plus vaginal radium, and uterine radium plus hysterectomy in stage I endometrial carcinoma.

From 1958 to 1967, a prospective randomized trial was conducted in 189 women with stage I, group I endometrial adenocarcinoma, comparing treatment by hysterectomy alone, preoperative uterine radium followed by hysterectomy, and hysterectomy and postoperative vaginal radium. All women have been followed for a minimum of 10 years. The actual survival rate at 5 years for all patients was 94.5% and at 10 years, 92.6%, with no statistical significance among the 3 treatment groups. Ther was also no statistical significance in survival rate in relation to size of uterine or myometrial invasion. There was a statistically significant difference in survival between grade I and grade III lesions (P less than 0.01) and between grade II and grade III lesions (P less than 0.05).

Adenocarcinoma

Radioactive artifacts: historical sources of modern radium contamination.

Radium has been distributed in a wide variety of devices during the early part of this century. Antique objects containing significant amounts of radium turn up at flea markets, antique shows, and antique dealers, in a variety of locations. These objects include radium in devices which were used by legitimate medical practitioners for legitimate medical purposes such as therapy, as well as a wide variety of "quack cures." These devices may contain anywhere from a few nanocuries to as much as several hundred microcuries of radium. In addition to medical sources, a large variety of scientific instruments utilize radium in luminous dials. These instruments include compasses, azimuth indicators, and virtually any object which might require some form of calibration. In addition, the consumer market utilized a large amount of radium in the production of wrist watches, pocket watches, and clocks with luminous dials. Some of these watches contained as much as 4.5 microCi of radium, and between 1913 and 1920 about 70 gm was produced for the manufacture of luminous compounds. In addition to the large amount of radium produced for scientific and consumer utilization, there were a number of materials produced which were claimed to contain radium but in fact did not, further adding to the confusion in this area. The wide availability of radium is a result of the public's great fascination with radioactivity during the early part of this century and a belief in its curative properties. A number of objects were produced in order to trap the emanations of radium in water for persons to drink in order to benefit from their healing effects. Since the late 20s and early 30s the public's attitude towards radiation has shifted 180 degrees and it is now considered an extremely dangerous and harmful material. However, even as late as the 1950s, there were still some items produced containing radioactivity which today would be unthinkable. The "Buck Rogers Mystery Ring" of the 1950s was activated with polonium. With the shift in public attitudes towards radioactivity, and increasing problems in disposal of radioactive materials, the disposal of radium presents a particularly perplexing problem. The radium which was produced in the early part of the century is still around in various forms and is extremely difficult to dispose of. All objects discovered claiming to contain radium should be taken seriously and should be properly surveyed.(ABSTRACT TRUNCATED AT 400 WORDS)

Equipment and Supplies

Radithor and the era of mild radium therapy.

Soon after the discovery of radium, a school of practitioners arose who were interested primarily in the physiological rather than the tumoricidal powers of this new radioactive element. This treatment philosophy was called "mild radium therapy" and involved the oral or parenteral administration of microgram quantities of radium and its daughter isotopes, often as cures for rheumatic diseases, hypertension, and metabolic disorders. Manufacturers of patent medicines responded to this market by producing a variety of over-the-counter radioactive preparations including pills, elixirs, and salves. One such nostrum was Radithor, a popular and expensive mixture of radium 226 and radium 228 in distilled water. Radithor was advertised as an effective treatment for over 150 "endocrinologic" diseases, especially lassitude and sexual impotence. Over 400,000 bottles, each containing over 2 muCi (74 kBq) of radium, were apparently marketed and sold worldwide between 1925 and 1930. The death of the Pittsburgh millionaire sportsman Eben M. Byers, who was an avid Radithor user, by radium poisoning in 1932 brought an end to this era and prompted the development of regulatory controls for all radiopharmaceuticals.

Alpha Particles

The metabolism of radium-226 during pregnancy in the rat.

Metabolism of radium including the transfer to the fetus through the placenta was studied during three successive pregnancies 92, 155, and 213 days after injection of 226Ra in young female rats. The cumulative fecal and urinary excretions of 226Ra in a 213-day period following injection were about 30 and 15% injected dose (%ID), respectively, most of them occurring during the first 42 days. The excretions were similar in both the pregnant and control (unmated) rats. The whole-body burden of radium (mostly in the skeleton) determined by actual analysis of the entire body was similar in the two groups and was about 53, 48, and 44 %ID at the first, second, and third pregnancy, respectively. Pregnancy alone, therefore, did not significantly affect metabolism of radium. At 20 days of gestation the mean placental content of radium was 0.005, 0.0045, and 0.0036 %ID in the first, second, and third litter, respectively; the corresponding mean fetal content was 0.01, 0.008, and 0.005 %ID. The radium burden of the full-term neonate (21-22 days) was 0.014 and 0.011 %ID for the first and second delivery, respectively. The total amount calculated of radium transferred from the mother to the 8-10 fetuses in a litter did not exceed about 0.3% of the maternal content per each pregnancy. Comparison of the ratio of radium and calcium in the fetus and maternal skeleton shows that there is a Ra-Ca discrimination during their passage from the mother to the fetus.

Animals

[The influence of radium therapie on the yeast contamination of the vagina (author's transl)].

Before the beginning of radium therapy a vaginal yeast contamination of 9,7% was found of 113 patients with different genital carcinomas. However, the incidence of vaginal yeast contamination increased suddenly to 30,9% under the contac irradiation therapy with radium. The radiation effect of radium is not sufficient for a "selfsterilisation" of the radium-carrier in the case of yeast contamination. Therefore, a chemic desinfection of the radium-carriers is principly necessary. The significance of radium therapy with respect to vaginal yeast contamination is discussed and the recommendation is made that routine mycological supervision be carried out on all patients with gynaecological carcinomas and appropriate antimycotic therapy initiated where necessary.

Adult

Radical hysterectomy with or without preoperative radium for stage IB squamous cell carcinoma of the cervix.

A retrospective study of 119 patients ranging from 30 to 69 years of age was undertaken to evaluate the effectiveness of preoperative radium treatment for patients with Stage IB (FIGO 1971) squamous cell carcinoma of the cervix undergoing radical hysterectomy. Results in 61 patients who had radical hysterectomy without preoperative radium treatment were compared to those in 58 patients who had received radium preoperatively. The patients receiving radium systems had an uncorrected 5-year survival rate of 89.7%, while the patients without preoperative radium treatment had a 75.1% 5-year rate of survival. This difference in survival rate was judged to be secondary to the greater incidence of lymphatic invasion and residual tumor in the surgical specimens of the patients who did not receive preoperative radium. The occurrence of significant gastrointestinal and urinary tract complications was identical in the 2 groups.

Adult

Phase II Randomized Trial of Radium-223 Dichloride and Cabozantinib in Patients With Renal Cell Carcinoma With Bone Metastases: RADICAL (Alliance A031801).

PURPOSE: Bone metastases (BM) occur in approximately 30% of patients with metastatic renal cell carcinoma (mRCC) and are associated with poor survival and symptomatic skeletal events (SSEs). Radium-223, an alpha-emitting bone-seeking radioisotope, and cabozantinib, a tyrosine kinase inhibitor, have demonstrated activity in BM. RADICAL (Alliance A031801; ClinicalTrials.gov identifier: NCT04071223) evaluated cabozantinib ± radium-223 in mRCC with BM. METHODS: This phase II trial enrolled patients with mRCC of any histology with ≥1 BM. Patients were randomly assigned 1:1 to cabozantinib ± radium-223, stratified by osteoclast-targeted therapy (OTT), prior therapy, opioid use, and International mRCC Database Consortium (IMDC) risk. The primary end point was SSE-free survival (SSE-FS). Secondary end points included safety, objective response rate (ORR), progression-free survival, and overall survival (OS). A target of 124 evaluable patients was planned, with a prespecified interim futility analysis at 50% of expected SSE-FS events; the trial would stop if the stratified hazard ratio (sHR) > 1.0. RESULTS: The prespecified interim futility analysis was conducted after 90 patients were enrolled and crossed the futility boundary, leading to closure at 98 patients. The final analysis included all 98 patients. Median age was 63 years, 82.7% had clear cell histology, and 79.6% were using an OTT. IMDC risk was favorable (18.4%), intermediate (67.3%), and poor (14.3%). Median follow-up was 13.1 months. Median SSE-FS for cabozantinib with radium-223 versus cabozantinib was 16.7 versus 17.6 months (sHR, 1.46 [90% CI, 0.86 to 2.51]). Median OS was 28.3 versus 19.7 months (sHR, 1.40 [95% CI, 0.70 to 2.79]). ORR was 19.4% versus 25.0% (P = .78). Grade ≥3 adverse events were similar across arms (69.6% v 75.5%). CONCLUSION: Radium-223 did not improve SSE-FS when added to cabozantinib. The combination demonstrated a manageable safety profile.

Humans