lead-radioisotopes and Lung-Neoplasms

Diffusing alpha-emitters radiation therapy (DART) is a proposed new form of brachytherapy, allowing the treatment of solid tumors by alpha particles. DART utilizes implantable sources carrying small activities of radium-224, which continually release into the tumor radon-220, polonium-216 and lead-212 atoms, while radium-224 itself remains fixed to the source. The released atoms disperse inside the tumor by diffusive and convective processes, creating, through their alpha emissions, a high-dose region measuring several mm in diameter about each source. The efficacy of DART has been demonstrated in preclinical studies on mice-borne squamous cell carcinoma and lung tumors and the method is now being developed toward clinical trials. This work studies DART safety with respect to the dose delivered to distant organs as a result of lead-212 leakage from the tumor through the blood, relying on a biokinetic calculation coupled to internal dose assessments. It is found that the dose-limiting organs are the kidneys and red bone marrow. Assuming a typical source spacing of approximately 5 mm and a typical radium-224 activity density of 0.4-0.8 MBq g(-1) of tumor tissue, it is predicted that tumors weighing up to several hundred grams may be treated without reaching the tolerance dose in any organ.

Topics: Alpha Particles; Animals; Bone Marrow; Brachytherapy; Carcinoma, Squamous Cell; Female; Humans; Kidney; Kinetics; Lead Radioisotopes; Lung Neoplasms; Male; Mice; Models, Biological; Radioisotopes; Radiometry; Radiotherapy Dosage; Radium

Diffusing alpha-emitters radiation therapy (DART) is a new form of brachytherapy enabling the treatment of solid tumors with alpha radiation. The present study examines the antitumoral effects resulting from the release of alpha emitting radioisotopes into solid lung carcinoma (LL2, A427, and NCI-H520).. An in vitro setup tested the dose-dependent killing of tumor cells exposed to alpha particles. In in vivo studies, radioactive wires (0.3 mm diameter, 5 mm long) with (224)Ra activities in the range of 21-38 kBq were inserted into LL/2 tumors in C57BL/6 mice and into human-derived A427 or NCI-H520 tumors in athymic mice. The efficacy of the short-lived daughters of (224)Ra to produce tumor growth retardation and prolong life was assessed, and the spread of radioisotopes inside tumors was measured using autoradiography.. The insertion of a single DART wire into the center of 6- to 7-mm tumors had a pronounced retardation effect on tumor growth, leading to a significant inhibition of 49% (LL2) and 93% (A427) in tumor development and prolongations of 48% (LL2) in life expectancy. In the human model, more than 80% of the treated tumors disappeared or shrunk. Autoradiographic analysis of the treated sectioned tissue revealed the intratumoral distribution of the radioisotopes, and histological analysis showed corresponding areas of necrosis. In vitro experiments demonstrated a dose-dependent killing of tumors cells exposed to alpha particles.. Short-lived diffusing alpha-emitters produced tumor growth retardation and increased survival in mice bearing lung tumor implants. These results justify further investigations with improved dose distributions.

Topics: Alpha Particles; Animals; Autoradiography; Brachytherapy; Dose-Response Relationship, Radiation; Humans; Lead Radioisotopes; Lung Neoplasms; Male; Mice; Mice, Inbred C57BL; Mice, Nude; Neoplastic Stem Cells; Radiotherapy Dosage; Radium; Thorium

The relation between increased risk of lung cancer and exposure to indoor radon is assessed in epidemiological studies. Both the quality and reliability of smoking data and the radon exposure data are of primary importance. Contemporary measurement of radon concentration in the dwellings of individuals in a case-control study is traditionally used to assess past history of radon exposure. These assessments are somewhat unreliable since presently measured radon concentration might not be representative for a given location long ago. The measurement of long-lived decay products from 222Rn remaining indoors on hard surfaces, such as glass, makes it possible to assess the exposure to indoor radon. At the Swedish Radiation Protection Institute, a combination of two different solid-state nuclear track detectors has been developed to assess the 210Pb activity implanted in glass surfaces by measuring 210Po alpha activity. This detector (a RETRO detector) is used in the Swedish radon epidemiological case-control study of non-smokers with the aim to provide an alternative estimate of individual radon exposure and to evaluate the usefulness of RETRO measurements. A total of 576 different objects were found and 568 were measured. For 225 individuals, we measured two personal objects that had been in the same person's possession for more than 20 years. The standard deviation of the average radon concentration obtained from these two objects had a median value of 13 Bq/m3 indicating a precision of exposure of approximately 20%. The correlation between 210Po surface activity measured earlier and the mean values of radon concentrations in a number of Swedish dwellings is used to estimate the historical, average radon concentration. This average correlation factor seems also to be valid for measurements in the non-smoker epidemiological study.

Topics: Air Pollutants, Radioactive; Air Pollution, Indoor; Air Pollution, Radioactive; Epidemiologic Methods; Glass; Housing; Humans; Lead Radioisotopes; Lung Neoplasms; Polonium; Radiometry; Radon; Retrospective Studies; Risk Factors; Surface Properties; Sweden

A preliminary case-control study of 19 lung cancer cases older than 55 y and 141 age-matched controls was carried out among a group of underground miners in Southern China who were exposed to 222Rn and its decay products. 210Pb activity levels were measured in the skull to estimate radon exposure. Radon exposure was also estimated in working level months, based on work histories and available industrial hygiene data. There was a smooth gradient of lung cancer risk with categories of skeletal 210Pb level at time of last radon exposure; relative risks of 1.0, 2.9, 3.2, and 4.7 for categories < 51.8, 51.8-77.7, 77.8-107.3, and > or = 107.4 Bq (< 1,400, 1,400-2,099, 2,100-2,899, and > or = 2,900 pCi), respectively. Relative risks were unaffected by adjustment for exposure to arsenic in the mine or by adjustment for working level months. Risks also increased with cumulative working level month exposure, but the gradient of risk lessened after adjustment for exposure to arsenic. 210Pb, at the time of last radon exposure (p = 0.13) and at the current 210Pb level (p = 0.01), was not highly correlated with the working level month estimate. Data were sparse but smoking had minimal effect on risk gradient with level of skeletal 210Pb activity. This study suggests measured 210Pb level may be a more precise predictor of lung cancer risk than working level month.

Topics: Case-Control Studies; China; Humans; Lead Radioisotopes; Lung Neoplasms; Male; Middle Aged; Mining; Neoplasms, Radiation-Induced; Radon; Skull; Tin