Production of sealed rod sources made from epoxy resin for the Saint-Petersburg brick phantom for the calibration of whole-body counters.

Rod sources are a common tool for the calibration of whole-body counters in combination with the Saint-Petersburg brick phantom. Here, a method for the production of such sources in ordinary radiochemical laboratories is presented. The rod sources consist of a tubular capsule of rigid polyvinyl chloride with a radioactive filling of epoxy resin. The method allows the production of rod sources at material costs of about 1 € per rod source and of ten rod sources by one person per day. Quality-assurance measurements were performed regarding the spatial distribution of the activity within the rod sources and the distribution of the activity throughout a set of sources. The relative double standard deviation of the activities of five different segments of single rod sources was 7.1%. The relative double standard deviation within a set of 90 rod sources was 2.8% after those 11% of sources with the greatest deviation from the arithmetic mean were discarded. Tests according to ISO 2919 to certify the rod sources as sealed sources of Class 2 of this standard were successfully conducted. The bending test proved to be the most critical test for the rod sources; the sources were broken by a mass of 12-14 kg, which is only slightly more than the stipulated mass of 10.2 kg. The presented method allows for a cost- and labour-effective production of sealed radioactive rod sources and thus facilitates the application of the Saint-Petersburg brick phantom for calibrations and interlaboratory comparisons of whole-body counters.

Analysis of EPR and FISH studies of radiation doses in persons who lived in the upper reaches of the Techa River.

Waterborne radioactive releases into the Techa River from the Mayak Production Association in Russia during 1949-1956 resulted in significant doses to about 30,000 persons who lived in downstream settlements. The residents were exposed to internal and external radiation. Two methods for reconstruction of the external dose are considered in this paper, electron paramagnetic resonance (EPR) measurements of teeth, and fluorescence in situ hybridization (FISH) measurements of chromosome translocations in circulating lymphocytes. The main issue in the application of the EPR and FISH methods for reconstruction of the external dose for the Techa Riverside residents was strontium radioisotopes incorporated in teeth and bones that act as a source of confounding local exposures. In order to estimate and subtract doses from incorporated (89,90)Sr, the EPR and FISH assays were supported by measurements of (90)Sr-body burdens and estimates of (90)Sr concentrations in dental tissues by the luminescence method. The resulting dose estimates derived from EPR to FISH measurements for residents of the upper Techa River were found to be consistent: The mean values vary from 510 to 550 mGy for the villages located close to the site of radioactive release to 130-160 mGy for the more distant villages. The upper bound of individual estimates for both methods is equal to 2.2-2.3 Gy. The EPR- and FISH-based dose estimates were compared with the doses calculated for the donors using the most recent Techa River Dosimetry System (TRDS). The TRDS external dose assessments are based on the data on contamination of the Techa River floodplain, simulation of air kerma above the contaminated soil, age-dependent lifestyles and individual residence histories. For correct comparison, TRDS-based doses were calculated from two sources: external exposure from the contaminated environment and internal exposure from (137)Cs incorporated in donors' soft tissues. It is shown here that the TRDS-based absorbed doses in tooth enamel and muscle are in agreement with EPR- and FISH-based estimates within uncertainty bounds. Basically, this agreement between the estimates has confirmed the validity of external doses calculated with the TRDS.

Preparation and preliminary studies on 177Lu-labeled hydroxyapatite particles for possible use in the therapy of liver cancer.

INTRODUCTION: Intra-arterial administration of particulates labeled with suitable beta(-)-emitting radionuclides has emerged as one of the most successful modality for the treatment of primary and metastatic liver cancer. (177)Lu [T(1/2)=6.73 d, E(beta)(max)=0.49 MeV, E(gamma)=208 keV (11%)] could be envisaged as a viable radionuclide for use in liver cancer therapy with wider acceptability owing to its feasibility of production in large-scale and relatively longer half-life providing logistic advantages. Hydroxyapatite (HA) particles of 20-60 microm size range are chosen as the particulate carrier due to its excellent biocompatibility and ease of labeling with lanthanides. METHODS: (177)Lu was produced by thermal neutron bombardment on enriched Lu target. HA particles of desired size range were synthesized and characterized. Radiolabeling of HA particles was achieved at room temperatures within 30 min. The biological behavior of (177)Lu-labeled HA particles prepared under optimized conditions was tested in Wistar rats. RESULTS: (177)Lu was produced with a specific activity of 444.2+/-41.8 GBq/mg and radionuclidic purity of 99.98%. (177)Lu-HA was prepared with high radiochemical purity of >99%, and the radiolabeled agent showed excellent in vitro stability. The agent exhibited approximately 73% retention of injected activity in liver after 14 days postadministration with insignificant uptake in any other major organ/tissue except skeleton in biodistribution and imaging studies. CONCLUSION: (177)Lu-HA exhibited promising features in radiochemical studies. However, preliminary biodistribution studies in normal Wistar rats exhibited suboptimum liver retention and an undesirable skeletal uptake.

Can the HML's sliced BOMAB phantom be used in any whole body counter with a reduced number of sources?

The sliced Bottle Manikin Absorber (BOMAB) phantom was originally proposed as an alternative to a commercially available phantom, but it suffers from the disadvantage of containing over 160 sources that need to be manufactured; however, it was found that the number of slices could be reduced substantially and that two slices in the sliced phantom gave the same performance characteristics over a wide energy range as a conventional BOMAB phantom for a particular counting system. This work explores the adaptability of this phantom to another counting geometry. The response of the Human Monitoring Laboratory's whole-body counter measuring this phantom with a decreasing number of planar sources has been modelled using MCNP5 over a wide energy range (122-2754 keV). It was found that the best agreement was obtained when the phantom contained 10 sources, 1 in the mid point of each section. As this is a different result from a previous finding, any other counting geometry will have to be assessed to determine the optimum loading if the sliced phantom is to be used. Also, it is clear that this type of phantom cannot be used for an intercomparison that will encounter different counting geometries, unless it contains a full loading of sources.

Long-circulating liposomes radiolabeled with [18F]fluorodipalmitin ([18F]FDP).

Synthesis of a radiolabeled diglyceride, 3-[(18)F]fluoro-1,2-dipalmitoylglycerol [[(18)F]fluorodipalmitin ([(18)F]FDP)], and its potential as a reagent for radiolabeling long-circulating liposomes were investigated. The incorporation of (18)F into the lipid molecule was accomplished by nucleophilic substitution of the p-toluenesulfonyl moiety with a decay-corrected yield of 43+/-10% (n=12). Radiolabeled, long-circulating polyethylene-glycol-coated liposomes were prepared using a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] ammonium salt (61:30:9) and [(18)F]FDP with a decay-corrected yield of 70+/-8% (n=4). PET imaging and biodistribution studies were performed with free [(18)F]FDP and liposome-incorporated [(18)F]FDP. Freely injected [(18)F]FDP had the highest uptake in the liver, spleen and lungs. Liposomal [(18)F]FDP remained in blood circulation at near-constant levels for at least 90 min, with a peak concentration near 2.5%ID/cc. Since [(18)F]FDP was incorporated into the phospholipid bilayer, it could potentially be used for radiolabeling a variety of lipid-based drug carriers.

Dose assessment for ingestion of a 330 kilobecquerel 60Co hot particle.

On leaving the irradiated fuel bay at Pickering A nuclear power station, a worker triggered a whole body monitor alarm with activity in or on his head, and despite careful decontamination techniques he subsequently swallowed a hot particle. Over the next 3 d, the radioactivity was tracked through the body. It was then excreted in a single faecal sample and recovered for physical and radiochemical analysis. This analysis demonstrated that the particle contained 330 kBq of 60Co and only traces of other radioactivity. Its dimensions were approximately 50-130 microm and its composition was consistent with that of Stellite 6. A dose assessment was carried out taking into account the residence time of the particle in the mouth and its transit through the body. The estimated committed effective dose was 1.4 mSv, and the equivalent dose to the maximally exposed 1 cm2 of skin, 81 mSv.

Development of an improved dose reconstruction system for the Techa River population affected by the operation of the Mayak Production Association.

The Techa River Dosimetry System (TRDS) has been developed to provide estimates of dose received by approximately 30,000 members of the Extended Techa River Cohort (ETRC). Members of the ETRC were exposed beginning in 1949 to significant levels of external and internal (mainly from (90)Sr) dose but at low to moderate dose rates. Members of this cohort are being studied in an effort to test the hypothesis that exposure at low to moderate dose rates has the same ability to produce stochastic health effects as exposure at high dose rates. The current version of the TRDS is known as TRDS-2000 and is the subject of this paper. The estimated doses from (90)Sr are supported strongly by approximately 30,000 measurements made with a tooth beta-particle counter, measurements of bones collected at autopsy, and approximately 38,000 measurements made with a special whole-body counter that detects the bremsstrahlung from (90)Y. The median doses to the red bone marrow and the bone surface are 0.21 and 0.37 Gy, respectively. The maximum doses to the red bone marrow and bone surface are 2.0 and 5.2 Gy, respectively. Distributions of dose to other organs are provided and are lower than the values given above. Directions for future work are discussed.

Retrospective dose assessment for the population living in areas of local fallout from the Semipalatinsk nuclear test site Part I: External exposure.

A short analysis of all 111 atmospheric events conducted at the Semipalatinsk Test Site (STS) in 1949-1962 with regard to significant off-site exposure (more than 5 mSv of the effective dose during the first year after the explosion) has been made. The analytical method used to assess external exposure to the residents living in settlements near the STS is described. This method makes use of the archival data on the radiological conditions, including the measurements of exposure rate. Special attention was given to the residents of Dolon and Kanonerka villages exposed mainly as a result of the first test, detonated on August 29, 1949. For the residents of those settlements born in 1935, the dose estimates calculated according to the analytical method, are compared to those derived from the thermoluminescence measurements in bricks and electron paramagnetic resonance measurements in teeth. The methods described in this paper were used for external dose assessment for the cohort members at an initial stage of an ongoing epidemiological study conducted by the U.S. National Cancer Institute in the Republic of Kazakhstan. Recently revised methods and estimates of external exposure for that cohort are given in another paper (Simon et al.) in this conference.

External dose estimates for Dolon village: application of the U.S./Russian joint methodology.

Methods to estimate external dose from radioactive fallout from nuclear tests have for many years depended on two types of data: measurements of exposure rate in air and an empirically derived power function to describe the change in exposure rate with time, Over the last four years, a working group with American and Russian participation has developed a bi-national joint methodology that offers an improved capability for estimating external dose. In this method, external dose is estimated using exposure rate functions derived from data from American nuclear tests similar in construction to SNTS (Semipalatinsk Nuclear Test Site) devices. For example, in this paper, we derive doses for test #1 (August 29, 1949) at the SNTS using an exposure rate function for the U.S. TRINITY test. For the case of test #1, the average external dose for a person in Dolon is estimated to have been about 0.5 Gy compared to 1 to 2 Gy estimated in other work. This prediction agrees better with reported EPR measurements in teeth from village residents and with measurements of TL signals in bricks from Dolon buildings. This report presents the basic elements of the joint methodology model for estimation of external dose received from SNTS fallout.

Kevlar® as a Potential Accident Radiation Dosimeter for First Responders, Law Enforcement and Military Personnel.

Today the armed forces and law enforcement personnel wear body armor, helmets, and flak jackets composed substantially of Kevlar® fiber to prevent bodily injury or death resulting from physical, ballistic, stab, and slash attacks. Therefore, there is a high probability that during a radiation accident or its aftermath, the Kevlar®-composed body armor will be irradiated. Preliminary study with samples of Kevlar® foundation fabric obtained from body armor used by the U.S. Marine Corps has shown that all samples evaluated demonstrated an EPR signal, and this signal increased with radiation dose. Based on these results, the authors predict that, with individual calibration, exposure at dose above 1 Gy can be reliably detected in Kevlar® samples obtained from body armor. As a result of these measurements, a post-event reconstruction of exposure dose can be obtained by taking various samples throughout the armor body and helmet worn by the same irradiated individual. The doses can be used to create a whole-body dose map that would be of vital importance in a case of a partial body or heterogeneous exposure.

ENHANCED RADIOACTIVE CONTENT OF 'BALANCE' BRACELETS.

During a routine whole body counting measurement of a worker at the Nuclear Research Center Negev, abnormal activities of (232)Th and (238)U were measured. After a thorough investigation, it was found that the radioactivity was due to a rubber bracelet ('balance bracelet') worn by the worker during the measurement. The bracelet was counted directly by an high pure germanium gamma spectrometry system, and the specific activities determined were 10.80 ± 1.37 Bq g(-1) for (232)Th and 5.68 ± 0.88 Bq g(-1) for natural uranium. These values are obviously high compared with normally occurring radioactive material (NORM) average values. The dose rate to the wrist surface was estimated to be ∼3.9 µGy h(-1) and ∼34 mGy for a whole year. The dose rate at the centre of the wrist was estimated to be ∼2.4 µGy h(-1) and ∼21 mGy for a whole year. The present findings stresses a more general issue, as synthetic rubber and silicone products are common and widely used, but their radioactivity content is mostly uncontrolled, thus causing unjustified exposure due to enhanced NORM radioactivity levels.

A cytogenetic follow-up of some highly irradiated victims of the Chernobyl accident.

A follow-up of 10 highly irradiated men, mostly reactor crew, from the Chernobyl accident is described. Their pre-accident medical conditions and relevant medical status approximately 10-13 y later are listed. A comparison is made between estimates of their average whole-body penetrating radiation doses derived from several biological parameters. First estimates were based on their presenting severity of prodromal sickness, early changes in blood cell counts and dicentric chromosome aberrations in lymphocytes. In three cases ESR measurements on tooth enamel were also made. Retrospective dosimetry using FISH translocations was attempted 10-13 y later. This showed good agreement for those patients with the lower earlier dose estimates, up to about 3 Gy. For the others, extending up to about 12 Gy, the translocations indicated lower values, suggesting that in these cases translocations had somewhat declined. Repeated chromosomal examinations during the follow-up period showed an expected decline in dicentric frequencies. The pattern of decline was bi-phasic with a more rapid first phase, with a half-life of approximately 4 months followed by a slower decline with half-lives around 2-4 y. The rapid phase persisted for a longer time in those patients who had received the highest doses. 10-13 y later dicentric levels were still above normal background, but well below the translocation frequencies.

A possible low intracellular potassium in obesity.

In comparison with lean marathon runners whose fat content was 15%, obese subjects with a fat content of 55% showed a 36% reduction in intracellular potassium. It is hypothesized that as much as 60% of this decrease may have been due to the lower proportion of muscle (which has the highest intracellular potassium of any tissue) in the fat free mass of very obese subjects. The remainder of the decrease seems to have been a measurement artefact owing to self-absorption of gamma rays by adipose tissue, most of which is distributed over potassium rich lean tissue. The low intracellular potassium values found in obesity should not be interpreted as necessarily signifying potassium deficiency.

Distribution of technetium-99m-labeled multilamellar liposomes in patients with Hodgkin's disease.

The distribution of 99mTc-labeled multilamellar liposomes composed of dimyristoyl phosphatidylcholine (DMPC) and dimyristoyl phosphatidylglycerol (DMPG) at a molar ratio of 7:3, administered intravenously, was studied in ten patients with Hodgkin's disease (HD). The dose of lipid was 150 mg/m2 and the mean dose of radioactivity injected per patient was 8.1 mCi (range 6.7-9.8). Whole-body imaging techniques were used, and for each organ an uptake index was calculated as the percent photographic density (PD) relative to the PD of the liver. Results were compared to those in a group of six patients with other malignancies. Increased liposome uptake in several skeletal areas was observed in one patient with HD with diffuse bone involvement and in the bone marrow of two patients with HD with bone marrow involvement. No definite liposome uptake was observed in lymph nodes involved by HD or in tumor areas of patients with other malignancies. Patients with HD had a significantly higher uptake by bone marrow (23.8% compared with 10.2% at 4 hr p = 0.02), and lungs (59.6% compared with 25.0% at 4 hr, p = 0.01) than patients with other malignancies. Among patients with HD, the uptake by bone marrow and lungs were higher in those with constitutional symptoms (bone marrow at 4 hr 31.4% compared with 16.2%, p = 0.02; lungs at 4 hr 68.8% compared with 50.4%, p = 0.19) and with liver involvement (bone marrow at 4 hr 30.8% compared with 16.8%, p = 0.03; lungs at 4 hr 73.6% compared with 45.6%, p = 0.03). These results suggest that patients with HD have a different pattern of distribution of multilamellar liposomes which may be related to a combination of nonspecific stimulation of the reticuloendothelial system and tumor uptake. It does not appear that liposomal 99mTc is capable of adequately imaging HD for clinical diagnosis.

Biodistribution of phospholipid vesicles in mice bearing Lewis lung carcinoma and granuloma.

Murine biodistributions of vesicle-encapsulated [111In]NTA were obtained under a number of conditions. These included normal animals, those bearing s.c.- or i.v.-implanted Lewis Lung Carcinoma (LLC) and those having both s.c.-LLC and sterile granuloma. Variations in the distributions were observed with a preinjection of unlabeled aminomannose (AM) vesicles or an increase in the labeled vesicle size. It was found that s.c. LLC exhibited uptake of between 10 and 25% injected dose/g (% ID/g) depending upon tumor mass with larger lesions having lower accumulation. Significant uptake enhancement (p less than 0.05) occurred after AM blockade. Similar results hold for the i.v.-injected LLC cells implying targeting to both primary and metastatic sites. By increasing vesicle size by a factor of 4, uptake by s.c. LLC declined to essentially blood levels; e.g., 2% ID/g. Granuloma accumulations were also at circulating values and, unlike s.c. LLC, could not be imaged.

Preliminary clinical study of the distribution of HPMA copolymers bearing doxorubicin and galactosamine.

Galactose-targeted delivery of macromolecules and drug conjugates to asialoglycoprotein receptor (ASGPR) positive cells has been widely documented in animals, although targeting in humans has never been demonstrated. In this study we report the pharmacokinetics and imaging determined in the first patient enrolled in a phase I clinical study of the poly[N-(2-hydroxypropyl)methacrylamide] copolymer bearing doxorubicin and galactosamine, known as PK2. Gradient high performance liquid chromatography (HPLC) evaluation of plasma and urine has been combined with 123I-based imaging to show biphasic clearance of the drug from the plasma (half-lives of 78+/-1 and 990+/-15), and approximately 30% delivery of the drug to the hepatic region, as determined by planar whole body imaging at 24 h. This patient has a multifocal hepatoma, and single photon emission computed tomography (SPECT) analysis showed a ratio of tumour tissue to normal liver uptake of approximately 1:3, at 24 h. On the basis of this patient, effective hepatic targeting can be achieved following an intravenous dose of 20 mg/m2 doxorubicin as PK2, however the therapeutic usefulness of this targeted drug has yet to be established.

[99mTc] liposomes for localizing experimental colitis in a rabbit model.

[(99m)Tc] liposomes (TL) and [(111)In]WBCs (WBCs) were compared for imaging colitis in rabbits. At 24 h, liver was the major organ of accumulation (7.8% TL vs 39.7% WBCs), besides blood (44.1% TL vs 24.4% WBCs) and spleen (0.3% TL vs 7% WBCs). The inflamed colon accumulated 37.1 times more of [(99m)Tc] liposomes than the normal colon whereas the ratio was only 15.2 in case of [(111)In] WBCs. The study demonstrates the usefulness of [(99m)Tc] liposomes for imaging inflammatory bowel diseases.

In vitro and in vivo characteristics of a human colon cancer cell line, SNU-C5N, expressing sodium-iodide symporter.

Rat NIS (rNIS) genes were transfected into a human colon cancer cell line (SNU-C5) by lipofection. The transfected cells (SNU-C5N) exhibited an increase 125I uptake to a level 10 times higher than the untransfected SNU-C5 cells. The addition of 300 microM DIDS, an anion channel blocker, to the culture media led to a 2.35 times increase of 125I uptake in the cells. For the first 10 minutes, up to 70% of the cellular radioactivity was released into the medium. In the biodistribution study using SNU-C5N-xenografted mice, the %ID/g of the SNU-C5N tumors at 1, 3, 6, and 12 h after the 125I injection were 4.43%, 1.09%, 1.05%, and 0.05%, respectively, which were significantly higher than those for the SNU-C5 tumors (P<0.05). In tumor imaging, the SNU-C5N-xenografted tumor was clearly visible. In this study, NIS lipofection is efficient for triggering significant iodide uptake by a nonthyroidal tumor. However, for an increased therapeutic effect, the key issue is iodide retention in the target tissue.

Anatomical distribution and sclerotic activity of bone metastases from thyroid cancer assessed with F-18 sodium fluoride positron emission tomography.

Currently, bone scintigraphy (BS) is considered to lack sensitivity in detecting bone metastases (BM) from thyroid cancer. We evaluated the anatomical distribution and metabolic behavior of BM as well as the accuracy of BS with and without combination of whole-body iodine scintigraphy (WBI) in detecting metastatic bone disease in thyroid carcinoma. F-18 positron emission tomography (PET), x-ray, BS, and WBI were performed in 35 patients with known or suspected bone metastases from papillary (9 patients) or follicular (26 patients) thyroid carcinoma. Twenty-two metastases were previously known in 14 patients. The indication was staging in 21 patients with high risk for BM, elevated thyroglobulin (Tg)-levels or evaluation of exact extent of BM (14 patients). In addition, results of WBI (35 patients), X-ray (35 patients) F-18 PET (35 patients), MRI of the spine (13 patients), and FDG-PET (15 patients) as well as the clinical course (1.5-4 years) were correlated. BM were detected in 18 patients. Solitary, bifocal, or multiple lesions were present in 9, 2, and 7 patients, respectively. The anatomical distribution of BM (n = 43) was as follows: spine, 42%; skull, 2%; thorax, 16%; femur, 9%; pelvis, 26%; humerus and clavicle, 5%. Sensitivity of BS in interpreting patients as positive or negative for having BM was 64%-85% (specificity, 95%-81%). The combination of BS and WBI was 100% sensitive in detecting metastatic bone disease. One patient had a single BM that was positive at BS but negative on WBI. All metastases were osteolytic on x-ray and two-thirds presented a missing or very limited osteosclerotic bone reaction on F-18 PET. Our data confirm the limited sensitivity of planar BS in detecting BM from thyroid cancer. The combination of BS and WBI, however, was highly accurate. Compared to other malignancies, the distribution pattern of BM presented a lower percentage of vertebral metastases and more patients with single metastases. Those findings in combination with a missing or only slight osteosclerotic bone reaction explain the limited sensitivity of planar BS alone.

Creation of two tomographic voxel models of paediatric patients in the first year of life.

Tomographic computational models, based on regional segmentation of CT or MRI medical images, have increasingly been proposed as replacements for current stylized mathematical models of human anatomy used in radiation dosimetry studies. While much effort has been devoted towards the creation of adult models, few research studies have been initiated to address the need for models supporting paediatric radiology dosimetry. In this study, two tomographic models were created using a combination of automatic and manual segmentation via a program created in-house using IDL version 5.5. The first model is of a normal 6 day female newborn, and consists of a 512 x 512 x 485 data array. The CT slices of this model were obtained every 1 mm, and 66 different anatomic regions were defined. The second model is of a patient developmentally equivalent to a 2 month male, and was saved as a 512 x 512 x 438 data array. This subject had severe tissue oedema within the gut, kidneys, liver and spleen. The model is thus considered representative of a critically ill child, from a patient subpopulation expected to receive a larger than normal number of diagnostic x-ray exams. The voxel volumes for the two models are 0.35 mm3 and 0.30 mm3, respectively, thus making these models the most detailed in existence for paediatric dosimetry applications. Ratios of organ masses for the UF newborn model to those within the reference ORNL/MIRD model range from highs of 1.2 to 1.7 for the oesophagus and small intestine/colon, respectively, to lows of 0.18 to 0.27 for the mandible and humeri, respectively. For the UF 2 month model, ratios of organ masses in the UF model to those in the 8 week GSF BABY model ranged from highs of 3.7 to 5.2 for the clavicles and spleen, respectively, to lows of 0.2 to 0.3 for the adrenals and scapulae, respectively.