-
Dose-response : a Publication of... Apr 2007The incident in London during November 2006 involving a lethal intake by Mr. Alexander Litvinenko of the highly-radioactive, alpha-particles-emitting polonium-210...
The incident in London during November 2006 involving a lethal intake by Mr. Alexander Litvinenko of the highly-radioactive, alpha-particles-emitting polonium-210 (Po-210) isotope, presumably via ingestion, sparked renewed interest in the area of Po-210 toxicity to humans. This paper is the result of assembling and interpreting existing Po-210 data within the context of what is considered a reliable risk model (hazard-function [HF] model) for characterizing the risk of death from deterministic effects of high alpha radiation doses and dose rates to body organs. The HF model was developed to address radiation exposure scenarios involving combined exposures to alpha, beta, and gamma radiations and can be used in circumstances where only one type of radiation is involved. Under a plausible but not yet validated set of assumptions and using available megabecquerel (Po-210) to gray dose-conversion factors, acute lethality risk vs. dose curves were developed for circumstances of ingestion exposure to Po-210 by humans. Initial risk calculations were carried out for a reference adult male human (a hypothetical 70-kg person). Results were then modified for application to all ages (except the in utero child) via the use of systemic Po-210 burden. Because of the unavailability of acute lethality data derived from human ingestions of high levels of Po-210, plausibility of risk calculations were evaluated based on data from studies of Po-210 injections in animals. The animal data, although limited, were found to be consistent with the theoretical risk calculations. Key findings are as follows: (1) ingestion (or inhalation) of a few tents of a milligram of Po-210 will likely be fatal to all exposed persons. (2) Lethal intakes are expected to involve fatal damage to the bone marrow which is likely to be compounded by damage caused by higher doses to other organs including the kidneys and liver. (3) Lethal intakes are expected to cause severe damage to the kidney, spleen, stomach, small and large intestines, lymph nodes, skin, and testes (males) in addition to the fatal damage to bone marrow. (4) The time distribution of deaths is expected to depend on the level of radioactivity ingested or inhaled, with deaths occurring within about a month after very high levels of radioactivity intake (e.g., systemic burdens > 1 MBq/kg-body-mass) and occurring over longer periods, possibly up to or exceeding a year for lower but lethal intakes (systemic burdens from 0.1 to 1.0 MBq/kg-body-mass). Below a systemic burden estimate of 0.02 MBq/kg-body-mass, deaths from deterministic effects are not expected to occur but the risk of cancer and for life shortening could be significant. New, funded experimental and modeling/theoretical research is needed to improve on these estimates.
PubMed: 18648599
DOI: 10.2203/dose-response.06-013.Scott -
The Indian Journal of Radiology &... Feb 2010The results of (18)F-fluorodeoxyglucose (FDG)-PET imaging carried out with the current standard techniques for assessment of urinary tract cancers have been reported to...
CONTEXT
The results of (18)F-fluorodeoxyglucose (FDG)-PET imaging carried out with the current standard techniques for assessment of urinary tract cancers have been reported to be less than satisfactory because of the urinary excretion of the tracer.
AIMS
To investigate the role of dual-phase FDG-PET/CT in the restaging of invasive cancers of the urinary bladder, with delayed imaging after forced diuresis and oral hydration as the scanning protocol.
SETTINGS AND DESIGN
FDG-PET has been considered to be of limited value for the detection of urinary tract cancers because of interference by the FDG excreted in urine. We investigated the efficacy of delayed FDG-PET/CT in the restaging of invasive bladder cancer, with imaging performed after intravenous (IV) administration of a potent diuretic and oral hydration.
MATERIALS AND METHODS
Twenty-nine patients with invasive cancer of the urinary bladder were included in this study. Patients were divided into two groups: Group I (22 patients) included cases with invasive bladder cancer who had not undergone cystectomy and group II (seven patients) included cases with invasive bladder cancer who had undergone cystectomy and urinary diversion procedure. All patients underwent FDG-PET/CT scan from the skull base to the mid-thighs 60 min after IV injection of 370 mega-Becquerel (MBq) of FDG. Additional delayed images were acquired 60-90 min after IV furosemide and oral hydration. PET/CT data were analyzed as PET and CT images studied separately as well as fused PET/CT images and the findings were recorded. The imaging findings were confirmed by cystoscopy, biopsy or follow-up PET/CT.
RESULTS
The technique was successful in achieving adequate washout of urinary FDG and overcame the problems posed by the excess FDG in the urinary tract. Hypermetabolic lesions could be easily detected by PET and precisely localized to the bladder wall, perivesical region and pelvic lymph nodes. PET/CT delayed images were able to demonstrate 16 intravesical lesions (in 13 patients), with excellent clarity. Lymph node metastases were detected in a total of six patients. Of these, in two patients, FDG-avid lymph nodes were evident only in the delayed images. The information provided by the postdiuretic delayed images changed the PET/CT interpretation in 14 patients of invasive bladder cancer: Recurrent bladder lesions were identified in 12 patients, pelvic lymph node metastasis (only) in one patient and bladder lesion as well as lymph node metastasis in one patient. Distant metastases were detected by PET/CT in two cases. CT scan was false-negative for early recurrence in the bladder wall for seven of 16 lesions. CT also showed two false-positive lesions. There were no false-positives with PET.
CONCLUSIONS
Detection of recurrent disease in cases of invasive bladder cancer can be significantly improved by using FDG-PET/CT, with delayed imaging following forced diuresis and oral hydration. Composite PET/CT is superior to CT alone for the restaging of invasive bladder cancers.
PubMed: 20351986
DOI: 10.4103/0971-3026.59746 -
Small (Weinheim An Der Bergstrasse,... Aug 2011Raman imaging offers unsurpassed sensitivity and multiplexing capabilities. However, its limited depth of light penetration makes direct clinical translation...
Raman imaging offers unsurpassed sensitivity and multiplexing capabilities. However, its limited depth of light penetration makes direct clinical translation challenging. Therefore, a more suitable way to harness its attributes in a clinical setting would be to couple Raman spectroscopy with endoscopy. The use of an accessory Raman endoscope in conjunction with topically administered tumor-targeting Raman nanoparticles during a routine colonoscopy could offer a new way to sensitively detect dysplastic lesions while circumventing Raman's limited depth of penetration and avoiding systemic toxicity. In this study, the natural biodistribution of gold surface-enhanced Raman scattering (SERS) nanoparticles is evaluated by radiolabeling them with (64) Cu and imaging their localization over time using micropositron emission tomography (PET). Mice are injected either intravenously (IV) or intrarectally (IR) with approximately 100 microcuries (μCi) (3.7 megabecquerel (MBq)) of (64) Cu-SERS nanoparticles and imaged with microPET at various time points post injection. Quantitative biodistribution data are obtained as % injected dose per gram (%ID g(-1)) from each organ, and the results correlate well with the corresponding microPET images, revealing that IV-injected mice have significantly higher uptake (p < 0.05) in the liver (5 h = 8.96% ID g(-1); 24 h = 8.27% ID g(-1)) than IR-injected mice (5 h = 0.09% ID g(-1); 24 h = 0.08% ID g(-1)). IR-injected mice show localized uptake in the large intestine (5 h = 10.37% ID g(-1); 24 h = 0.42% ID g(-1)) with minimal uptake in other organs. Raman imaging of excised tissues correlate well with biodistribution data. These results suggest that the topical application of SERS nanoparticles in the mouse colon appears to minimize their systemic distribution, thus avoiding potential toxicity and supporting the clinical translation of Raman spectroscopy as an endoscopic imaging tool.
Topics: Animals; Copper Radioisotopes; Endoscopy; Female; Mice; Mice, Nude; Microscopy, Electron, Transmission; Nanoparticles; Positron-Emission Tomography; Spectrum Analysis, Raman
PubMed: 21608124
DOI: 10.1002/smll.201002317 -
Journal of Nuclear Medicine : Official... Dec 2010Current SPECT radioligands available for in vivo imaging of the dopamine transporter (DAT) also show affinity for monoamine transporters other than DAT, especially the... (Comparative Study)
Comparative Study Randomized Controlled Trial
UNLABELLED
Current SPECT radioligands available for in vivo imaging of the dopamine transporter (DAT) also show affinity for monoamine transporters other than DAT, especially the serotonin transporter (SERT). The effect of this lack of selectivity for in vivo imaging is unknown. In this study, we compared the SPECT radioligands (123)I-2-β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)nortropane ((123)I-FP-CIT) and (123)I-N-(3-iodoprop-2E-enyl)-2-β-carbomethoxy-3β-(4-methylphenyl) nortropane ((123)I-PE2I), which has a 10-fold higher selectivity than (123)I-FP-CIT for DAT versus SERT [corrected].
METHODS
Sixteen healthy individuals were scanned in random order with both radioligands. The radioligands were administered according to standard recommendations: (123)I-FP-CIT was given as a bolus injection, and the ratio between the striatum and reference tissue was measured after 3 h. (123)I-PE2I was administered in a bolus-infusion setup, and the nondisplaceable binding potential (BP(ND)) was measured after 2 h. To assess the contribution of SERT to the overall SPECT signal, SERT was blocked by intravenous citalopram in 6 of the individuals.
RESULTS
The striatum-to-reference ratio - 1 of (123)I-FP-CIT was on average 18% higher than the striatal BP(ND) of (123)I-PE2I. Equal doses of radioactivity resulted in 3 times higher counting rates for (123)I-FP-CIT than for (123)I-PE2I, both in target and in reference brain regions. Citalopram infusion led to significant reductions in both striatal (22.8% ± 20.4%, P < 0.05) and thalamic (63.0% ± 47.9%, P < 0.05) (123)I-FP-CIT binding ratios, whereas BP(ND) of (123)I-PE2I was unaltered. Likewise, blocking of SERT led to increased (21% ± 30.1%, P < 0.001) plasma (123)I-FP-CIT, probably as a result of significant blocking of peripheral SERT binding sites. By contrast, plasma (123)I-PE2I remained stable.
CONCLUSION
(123)I-FP-CIT and (123)I-PE2I had approximately the same target-to-background ratios, but per injected megabecquerel, (123)I-FP-CIT gave rise to 3-fold higher cerebral counting rates. We found that (123)I-FP-CIT, but not (123)I-PE2I, brain images have a highly interindividual but significant signal contribution from SERT. Whether the SERT signal contribution is of clinical importance needs to be established in future patient studies.
Topics: Adult; Aged; Binding, Competitive; Brain; Citalopram; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Neostriatum; Nortropanes; Protein Binding; Radiopharmaceuticals; Scintillation Counting; Serotonin Plasma Membrane Transport Proteins; Selective Serotonin Reuptake Inhibitors; Tomography, Emission-Computed, Single-Photon; Tropanes; Young Adult
PubMed: 21078806
DOI: 10.2967/jnumed.110.078337 -
Molecular Therapy : the Journal of the... Apr 2011We recently demonstrated tumor-selective iodide uptake and therapeutic efficacy of radioiodine in neuroblastoma tumors after systemic nonviral polyplex-mediated sodium...
We recently demonstrated tumor-selective iodide uptake and therapeutic efficacy of radioiodine in neuroblastoma tumors after systemic nonviral polyplex-mediated sodium iodide symporter (NIS) gene delivery. In the present study, we used novel polyplexes based on linear polyethylenimine (LPEI), polyethylene glycol (PEG), and the synthetic peptide GE11 as an epidermal growth factor receptor (EGFR)-specific ligand to target a NIS-expressing plasmid to hepatocellular carcinoma (HCC) (HuH7). Incubation of HuH7 cells with LPEI-PEG-GE11/NIS polyplexes resulted in a 22-fold increase in iodide uptake, which was confirmed in other cancer cell lines correlating well with EGFR expression levels. Using (123)I-scintigraphy and ex vivo γ-counting, HuH7 xenografts accumulated 6.5-9% injected dose per gram (ID/g) (123)I, resulting in a tumor-absorbed dose of 47 mGray/Megabecquerel (mGy/MBq) (131)Iodide ((131)I) after intravenous (i.v.) application of LPEI-PEG-GE11/NIS. No iodide uptake was observed in other tissues. After pretreatment with the EGFR-specific antibody cetuximab, tumoral iodide uptake was markedly reduced confirming the specificity of EGFR-targeted polyplexes. After three or four cycles of polyplex/(131)I application, a significant delay in tumor growth was observed associated with prolonged survival. These results demonstrate that systemic NIS gene transfer using polyplexes coupled with an EGFR-targeting ligand is capable of inducing tumor-specific iodide uptake, which represents a promising innovative strategy for systemic NIS gene therapy in metastatic cancers.
Topics: Cell Line, Tumor; ErbB Receptors; Genetic Therapy; Humans; Iodine Radioisotopes; Liver Neoplasms; Polyethylene Glycols; Polyethyleneimine; Polymerase Chain Reaction; Polymers; Symporters
PubMed: 21245850
DOI: 10.1038/mt.2010.296 -
Plant Physiology Jun 1988In normal growth conditions, total protein percent (salt soluble plus hordein fractions) in the endosperm at maturity in barley cultivar Hordeum vulgare L. cv ;Ruth' was...
In normal growth conditions, total protein percent (salt soluble plus hordein fractions) in the endosperm at maturity in barley cultivar Hordeum vulgare L. cv ;Ruth' was about 14%, whereas in an accession of wild barley, Hordeum spontaneum Koch line 297, it was about 28%. Spike culture experiments were conducted to ascertain whether there were basic differences between the two genotypes under conditions of widely different nitrogen supply. Spikes of each genotype were grown from 8 to 25 days after flowering in in vitro culture in a growth medium containing 0 to 4 grams per liter nitrogen supplied as NH(4)NO(3). Spikes were pulse-labeled at intervals from 12 to 24 days after flowering with 3.7 megabecquerel of [(3)H]leucine to determine relative rates of synthesis of hordein-1 and hordein-2 polypeptides. At low nitrogen levels ;Ruth' had a lower protein content than 297, but at increasing nitrogen levels its protein content increased rapidly and reached a maximum (35%) higher than 297 (30%). The relative contribution of the hordein fraction to total protein increased mainly with time, and hordein-1 to total hordein increased mainly with nitrogen level, in both genotypes. There appeared to be no fundamental limitations in the capacity of ;Ruth' to accumulate protein; 297 appears to have a greater basal level of nitrogen availability under normal conditions.
PubMed: 16666176
DOI: 10.1104/pp.87.2.523