Biodistribution and Tumors MRI Contrast Enhancement of Magnetic Nanocubes, Nanoclusters, and Nanorods in Multiple Mice Models.

Magnetic resonance imaging (MRI) is a powerful technique for tumor diagnostics. Iron oxide nanoparticles (IONPs) are safe and biocompatible tools that can be used for further enhancing MR tumor contrasting. Although numerous IONPs have been proposed as MRI contrast agents, low delivery rates to tumor site limit its application. IONPs accumulation in malignancies depends on both IONPs characteristics and tumor properties. In the current paper, three differently shaped Pluronic F-127-modified IONPs (nanocubes, nanoclusters, and nanorods) were compared side by side in three murine tumor models (4T1 breast cancer, B16 melanoma, and CT26 colon cancer). Orthotopic B16 tumors demonstrated more efficient IONPs uptake than heterotopic implants. Magnetic nanocubes (MNCb) had the highest r2-relaxivity in vitro (300 mM-1·s-1) compared with magnetic nanoclusters (MNCl, 104 mM-1·s-1) and magnetic nanorods (MNRd, 51 mM-1·s-1). As measured by atomic emission spectroscopy, MNCb also demonstrated better delivery efficiency to tumors (3.79% ID) than MNCl (2.94% ID) and MNRd (1.21% ID). Nevertheless, MNCl overperformed its counterparts in tumor imaging, providing contrast enhancement in 96% of studied malignancies, whereas MNCb and MNRd were detected by MRI in 73% and 63% of tumors, respectively. Maximum MR contrasting efficiency for MNCb and MNCl was around 6-24 hours after systemic administration, whereas for MNRd maximum contrast enhancement was found within first 30 minutes upon treatment. Presumably, MNRd poor MRI performance was due to low r2-relaxivity and rapid clearance by lungs (17.3% ID) immediately after injection. MNCb and MNCl were mainly captured by the liver and spleen without significant accumulation in the lungs, kidneys, and heart. High biocompatibility and profound accumulation in tumor tissues make MNCb and MNCl the promising platforms for MRI-based tumor diagnostics and drug delivery.

Risk of Hematologic Malignancies in the Offspring of Female Workers of the Mayak Nuclear Facility in the Southern Urals, Russian Federation.

Long-term effects of in utero exposure to ionizing radiation remain poorly quantified in humans. In this study, the risk of hematologic malignancies was investigated in offspring of female workers of the Mayak Production Association, a large Russian nuclear facility. Excess relative risks (ERR) for exposure to gamma radiation and plutonium were estimated in a cohort of 8,466 offspring who were born between January 1, 1948 and December 31, 1988 and followed until 2009. An unstable linear ERR of 1.12 (95% CI 0.11-3.44) per 100 mGy gamma exposure in utero was estimated based on 32 incident hematologic malignancies in 277,002 person-years under risk. The ERR was increased in the dose category 20-79 mGy gamma exposure in utero (1.75, 95% CI 0.04; 5.63), while the other dose categories showed decreased or unstable estimates. Leukemia showed an ERR of 1.76 (95% CI 0.01-8.33) per 100 mGy based on 13 cases. There was no consistent association with plutonium exposure. While an increased risk of hematologic malignancies after gamma exposure in utero was suggested, the small numbers prevented more definitive conclusions.

Risk of solid cancer in the offspring of female workers of the Mayak nuclear facility in the Southern Urals, Russian Federation.

Studies of cancer risk following in utero exposure to ionizing radiation are limited in number, particularly for adult-onset cancers, and the evidence is unclear. In the present study, the risk of solid cancer incidence following in utero radiation exposure is examined among 8466 offspring of female nuclear workers at one of the largest nuclear facilities (Mayak Production Association) in the Russian Federation. Poisson regression methods were used to estimate excess relative risks (ERRs) per Gray (Gy). Mother's uterine gamma dose served as a surrogate for fetal gamma dose. During 277,002 person-years of follow-up (1948-2009), there were 177 first primary solid cancers excluding non-melanoma skin cancers. Estimated in utero gamma and plutonium doses exceeded zero for 41 and 23 % of offspring, respectively. Of the 177 solid cancers, 66 occurred among individuals with some in utero exposure to gamma radiation and 53 among those with estimated plutonium exposures. There was no indication of a statistically significantly increased risk of solid cancer incidence from in utero gamma exposure (linear ERR/Gy -1.0; upper 95 % confidence limit 0.5). This result was unchanged after accounting for subsequent occupational exposure. Plutonium doses were estimated but were too low to obtain meaningful risk estimates. Thus, in this cohort in utero radiation exposure was not associated with solid cancer risk. This is consistent with an earlier report of mortality in the cohort, but is based on twice as many cases and less susceptible to biases inherent in mortality analyses. Given the relatively young age of the cohort with respect to cancer, continued follow-up should be done as the number of cancer cases increases.

Cancer mortality following in utero exposure among offspring of female Mayak Worker Cohort members.

Little is known about long-term cancer risks following in utero radiation exposure. We evaluated the association between in utero radiation exposure and risk of solid cancer and leukemia mortality among 8,000 offspring, born from 1948-1988, of female workers at the Mayak Nuclear Facility in Ozyorsk, Russia. Mother's cumulative gamma radiation uterine dose during pregnancy served as a surrogate for fetal dose. We used Poisson regression methods to estimate relative risks (RRs) and 95% confidence intervals (CIs) of solid cancer and leukemia mortality associated with in utero radiation exposure and to quantify excess relative risks (ERRs) as a function of dose. Using currently available dosimetry information, 3,226 (40%) offspring were exposed in utero (mean dose = 54.5 mGy). Based on 75 deaths from solid cancers (28 exposed) and 12 (6 exposed) deaths from leukemia, in utero exposure status was not significantly associated with solid cancer: RR = 0.94, 95% CI 0.58 to 1.49; ERR/Gy = -0.1 (95% CI < -0.1 to 4.1), or leukemia mortality; RR = 1.65, 95% CI 0.52 to 5.27; ERR/Gy = -0.8 (95% CI < -0.8 to 46.9). These initial results provide no evidence that low-dose gamma in utero radiation exposure increases solid cancer or leukemia mortality risk, but the data are not inconsistent with such an increase. As the offspring cohort is relatively young, subsequent analyses based on larger case numbers are expected to provide more precise estimates of adult cancer mortality risk following in utero exposure to ionizing radiation.

Mayak workers study cohort. An inter-institutional comparison of causes of death in the cause-of-death register of Ozyorsk in the Russian Federation.

BACKGROUND: The cause-of-death register at the Southern Urals Biophysics Institute (SUBI), Ozyorsk, Russia, was established to document the number and causes of deaths in the Mayak workers cohort, which includes all persons (N = 22,377) employed at Mayak nuclear facility between 1948 and 1982. Most workers were occupationally exposed to high doses of ionizing radiation and have been shown to have increased risks of various chronic diseases including cancer. OBJECTIVES: To investigate the quality of cause of death coding in the SUBI register. METHODS: A random sample of 246 deaths (~1% of the total) was coded independently at the SUBI and the Danish Cancer Society using the International Classification of Diseases 9 (ICD-9). Proportions of matching codes were calculated. RESULTS: Overall, 233 deaths (95%) were identically classified using the ICD-9 main category matching. Excluding mismatches that were considered to be incorrectly coded during validation, the validity of the register increased to 98%. Using the specific ICD-9 first three-digit matching, 182 deaths were identically coded (74%) and the respective validity of the register was 85%. There were also some non-resolvable discrepancies demonstrating limitations of assigning one code for each death or using language-adapted ICD-9 version. CONCLUSIONS: This validation study was an important quality check of a register used for mortality follow-up in a highly influential epidemiological study on radiation-related health effects. The results of the inter-institutional comparison were generally favourable; however, since the comparison revealed individual mismatches and some systematically differing coding practices, it is essential to repeat it on a regular basis in order to maintain a high quality.