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Ventilation studies with krypton-81m.

Nuclear medicine offers well-established methods for regional lung function assessment in the preoperative evaluation of patients with lung disease. The perfusion study with Tc-99m macroaggregates is simple and can be performed without special precautions in radiation shielding. The ventilation study with Xe-133, however, requires more elaborate apparatus as well as special procedures to collect the exhaled radioactive rare gas. Nuclear medicine departments with access to short-lived radionuclides from a nearby cyclotron can use the krypton isotope Kr-81m. The physical half-life of Kr-81m is 13 s. Its gamma energy of 190 keV is optimal for gamma cameras. Kr-81m can be used as a medical isotope in spite of its short half-life. It can be eluted with a continuously flowing gas from the generator containing the mother nuclide Rb-81 which has half-life of 4.6 h. This short half-life not only simplifies radiation protection but allows repeated studies in different projections as well. Examples of comparative studies with Xe-133 and Kr-81m are presented. The importance of taking not only anterior and posterior pictures but also lateral oblique views is stressed.

Half-Life↗

Radionuclide imaging clinical study. Corporeal 133Xe washout for detecting venous leakage in impotence.

A quantitative test, corporeal 133Xe washout, was developed to detect venogenic impotence. Data were acquired in frame mode after intracorporeal injection of 0.1 ml (1-2 mCi or 37-74 MBq) of 133Xe in saline on one side of the midline just behind the glans in the flaccid state for 20 min. A time-activity curve (TAC) was generated from the region of interest (ROI) at the site of injection and a computer routine was then used to calculate clearance half-time (T1/2) in minutes and flow rate (Q) in ml/100 g tissue/min from corporeal 133Xe clearance. The data from 12 controls and 21 patients with venous leakage were analysed. In patients with venogenic impotence, T1/2 (mean +/- S.D.) was greatly increased (24.4 +/- 10.7 min vs 10.7 +/- 4.6 min in controls, P less than 0.005) whereas Q markedly decreased (2.4 +/- 1.3 ml/100 g tissue/min vs 5.4 +/- 2.3 ml/100 g tissue/min in controls, P less than 0.005). The sensitivity and specificity for detecting venous leakage at the optimal threshold of T1/2 equal to 13 min and Q equal to 3.7 ml/100 g tissue/min were 95 and 75%, respectively. The corporeal 133Xe clearance half-time and flow rate are two simple and clinically useful indices for detecting venous leakage.

Adult↗

The standardization of 62Cu and experimental determinations of dose calibrator settings for generator-produced 62CuPTSM.

The Positron Emission Tomography agent 62Cu Pyruvaldehyde Bis(N4-methyl)thiosemicarbazone (PTSM) has been standardized by the National Institute of Standards and Technology (NIST) using 4 pi beta liquid scintillation counting with 3H-standard efficiency tracing. Using a measurement model developed at NIST for the determination of experimental dose calibrator dial settings for short-lived radionuclides, the correct dial settings for 62CuPTSM in a clinically useful geometry (a 35 ml plastic syringe containing 33 ml of solution) as well as the standard NIST 5 ml glass ampoule have been elucidated. This measurement model is fully described, as is the treatment of associated uncertainties. The correct instrument settings for the NIST Capintec CRC-12 re-entrant ionization chamber ('dose calibrator') were found to be '499 +/- 6' and '489 +/- 8', respectively, for the syringe and ampoule geometries. The stated uncertainties are expanded (k = 2) uncertainties. The expanded uncertainties in the measured activity arising from these new dial settings are +/- 0.8% and +/- 1.4%, respectively, for the syringe and ampoule. The measured activities using these settings are lower than those obtained from the manufacture's recommended setting of '448' by 9.7% for the syringe and 7.7% for the ampoule, and underscore the need for experimental verification of the dose calibrator settings for each radionuclide and each geometry used in the clinic.

Calibration↗

Animal models of malignant mesothelioma.

Animal models of diffuse malignant mesothelioma have historically been used to assess carcinogenicity of various fiber types and to study the pathogenesis of this unusual neoplasm. Pleural and peritoneal mesotheliomas have been induced in rodents following exposure to erionite or asbestos fibers, radionuclides, particulate nickel compounds, and chemicals such as 3-methylcholanthrene. The role of SV40 virus as a cofactor with asbestos fibers in the development of diffuse malignant mesotheliomas in humans has been explored in animal models. SV40 virus alone induces mesotheliomas in hamsters. Generation of new transgenic mouse strains with targeted expression of SV40 large T and small t antigens in the mesothelium would be very useful for mechanistic studies. Human malignant mesotheliomas frequently show hypermethylation or deletions at the Cdkn2a/Arf and Cdkn2b gene loci and deletions or mutations at the NF2 gene locus. Heterozygous Nf2 (+/-) mice exposed to crocidolite asbestos fibers exhibited accelerated development of malignant mesotheliomas compared to wild-type littermates. Loss of the wild-type Nf2 allele, leading to biallelic inactivation, was observed in nine mesothelioma cell lines derived from Nf2 (+/-) mice. Similar to human malignant mesotheliomas, tumors from Nf2 (+/-) mice showed frequent homozygous deletions of the Cdkn2a/Arf locus and adjacent Cdkn2b tumor suppressor gene. As in the human disease, murine mesotheliomas also showed constitutive activation of Akt. This murine model of asbestos carcinogenesis recapitulates the molecular and histopathological features of the human disease and has significant implications for preclinical testing of novel preventive or therapeutic modalities.

Animals↗

Management of mixed wastes from biomedical research.

Mixed radioactive and chemical wastes generated by biomedical research were characterized, and various treatment methods for reducing their volume were evaluated. These wastes consist primarily of organic solvents used in the extraction and purification of radiolabeled biomolecules that are contaminated with low levels of the long-lived radionuclides, 3H and 14C. The Rockefeller University's mixed wastes fall into three broad chemical categories: phenol/chloroform, acetonitrile/water, and mixtures of miscellaneous solvents such as carbon tetrachloride, benzene, and other hazardous chemicals. Currently, with the exception of liquid scintillation cocktails (deregulated in 1981), there are no commercial disposal outlets for mixed wastes nor may they be stored legally for more than 90-180 d. Most of these mixed wastes can be effectively rendered into nonradioactive chemical and aqueous radioactive waste, both of which can be disposed of in accordance with existing regulations. However, to do so requires a Resource Conservation and Recovery Act (RCRA) Part B permit for licensure as a treatment, storage, and disposal facility. For many university research facilities, this may require financial and personnel resources disproportionate to the small amounts of waste produced. Also, such treatment, if not done properly, presents potential occupational hazards from the direct handling of waste materials. Deregulation of certain mixed wastes would be the safest, most cost-effective, and practical method for dealing with many mixed wastes of biomedical origin. In any event, a national regulatory solution must be found.

Hazardous Substances↗

Site-specific parameter values for the Nuclear Regulatory Commission's food pathway dose model.

Routine operations at the Savannah River Site (SRS) in Western South Carolina result in radionuclide releases to the atmosphere and to the Savannah River. The resulting radiation doses to the off-site maximum individual and the off-site population within 80 km of the SRS are estimated on a yearly basis. These estimates are currently generated using dose models prescribed for the commercial nuclear power industry by the Nuclear Regulatory Commission (NRC). The NRC provides default values for dose-model parameters for facilities without resources to develop site-specific values. A survey of land- and water-use characteristics for the Savannah River area has been conducted to determine site-specific values for water recreation, consumption, and agricultural parameters used in the NRC Regulatory Guide 1.109 (1977) dosimetric models. These site parameters include local characteristics of meat, milk, and vegetable production; recreational and commercial activities on the Savannah River; and meat, milk, vegetable, and seafood consumption rates. This paper describes how parameter data were obtained at the Savannah River Site and the impacts of such data on off-site dose. Dose estimates using site-specific parameter values are compared to estimates using the NRC default values.

Food Contamination, Radioactive↗

Ratio of hepatic arterial-to-portal venous blood flow--validation of radionuclide techniques in an animal model.

The ratio of hepatic arterial-to-portal venous blood flow can be determined from the analysis of a first-pass bolus through the liver by a number of techniques. This study examines the validity of four radiotracer techniques in an animal model. Thirty-four flow studies (3 mCi 99mTc-DTPA/study) were performed in seven anesthetized pigs. Images were acquired for 200 sec and time-activity curves were generated from lung, liver and kidney ROIs. These curves were analyzed using a slope-based (HPI), a height-based (mHAR) and two deconvolution-based methods employing exponential or gamma variate fits. There was an excellent correlation (r greater than 0.9) between results obtained with flow probes and the radiotracer techniques, with the exception of the HPI technique (r = 0.75). The mHAR and deconvolution techniques were inaccurate at very low and high arterial flows, due respectively to noise limitations and hemodynamic instability in the animal. Nevertheless, these techniques appear to be the most promising for routine clinical use.

Animals↗

Cardiovascular nuclear medicine: a progress report.

Providing insights into the functional state of the myocardium not available from other techniques, cardiovascular nuclear medicine is being applied more and more in coronary care units, where it makes possible frequent monitoring of function, and in exercise testing of outpatients. In addition, a nuclear "stethoscope" that generates a left ventricular volume curve may soon bring this valuable resource into office practice.

Cardiomegaly↗

Recombinant human thyrotropin in thyroid cancer and hypopituitarism due to sella metastasis.

We present a patient with thyroid cancer and hypopituitarism who required recombinant human thyrotropin (rhTSH) for 131I scanning with respect to subsequent therapy. The thyroid cancer had been unknown until central neurological symptoms developed, leading to the diagnosis of a huge metastasis to the sella that was the only manifestation of metastatic spread. The failure to generate endogenous thyrotropin (TSH) was overcome by the use of rhTSH for performing a 131I test. Unfortunately, the 131I uptake was not sufficient for therapy. This subject is the first reported case who required the application of rhTSH due to a single thyroid cancer metastasis in the sella region with secondary failure to generate endogenous TSH.

Aged↗

Transgenerational carcinogenesis: induction and transmission of genetic alterations and mechanisms of carcinogenesis.

Parental exposure, i.e. germ cell exposure to radiation and chemicals, increased the incidence of tumors and malformations in the offspring, and the germ-line alterations that cause cancer are transmissible to further generations. However, tumor incidences were 100-fold higher than those of ordinary mouse mutations and there were apparent strain differences in the types of induced tumors. In human, higher risk of leukemia is reported in the children of fathers who had been exposed to radionuclides at the nuclear reprocessing plants or to diagnostic doses of radiation. However, these findings in mice and men have not been confirmed in the children of atomic bomb survivors in Hiroshima and Nagasaki. Another important finding was that germ-line exposure was very weakly tumorigenic by itself. However, the transmissible alterations caused persistent hypersensitivity to tumor induction in the offspring, e.g. enhanced by postnatal treatment with tumor promoting/carcinogenic agents. The above results suggest that transmissible alterations might be imprinted in germ cells for the future development of cancer by the postnatal environment. Many gene loci concerning immunological, biochemical and physiological function might be involved, and the cumulative changes in such genes may slightly elevate or enhance tumor incidences, although mutations of tumor suppressor genes such as p53 were also detected in some offspring and genomic instability may modify tumor occurrence in transgenerational manner. In fact, Gene Chip analysis showed suppression and/or over-expression of many functional genes rather than cancer-related genes in the preconceptionally irradiated cancer prone progeny.

Animals↗

[Electronic spectral study on salicylaldehyde-amino acid Schiff bases in water].

Seven salicylaldehyde-amino acid Schiff bases in water were investigated by means of electronic spectra, which is helpful to investigate the label of radionuclides with the seven ligands in water for radiopharmaceutical study. Except 10(-5) mol x L(-1) for Sal-tyr, the minimum concentration of formation is 10(-4) mol x L(-1) for all other Sal-aas. Only Sal-his is generated at pH 9-10, while the minimum pH conditions for formation are 8 for Sal-gly and Sal-tyr, and 9 for other four. All Sal-aa but Sal-cys, whose concentration at 36 h is higher than that of newly produced one, decompose gradually since generation, with existing time of 24 h for Sal-gly and Sal-glu, and 48 h for other four.

Aldehydes↗

Correlation of Cu(PTSM) localization with regional blood flow in the heart and kidney.

In a dog model of myocardial ischemia, i.v. injection of [67Cu]Cu(PTSM) leads to an excellent linear correlation for both the heart and kidney between regional tissue radiocopper concentration and regional blood flow measured by radioactive micropheres. The 62Cu-labeled complex may serve as a generator-produced position-emitting perfusion tracer for these organs.

Animals↗

Myocardial perfusion imaging using thallium-201: a new algorithm for calculation of background activity.

A method is presented for calculating a background image to be subtracted from TI-201 myocardial perfusion images. The method was derived from experimental measurements of background components in which hearts of animals injected with TI-201 were replaced with hearts from nonradioactive animals. The algorithm generates a background image that accounts for TI-201 activity in surrounding tissues and within the cardiac chamber. Comparison of the computer-generated background images with background images of the experimental models showed a mean difference of about 3% (range 1-6%). Clinical images using this method of background generation and subtraction are presented.

Animals↗

Labeling and comparative biodistribution of the monoclonal antibody KS1/4 in nude mice bearing human lung adenocarcinoma.

In order to evaluate some of the key factors that may allow the optimization of radiolabeled monoclonal antibodies for use as diagnostic and therapeutic tools to detect and treat human neoplasia, we compared the biodistribution of the anti-lung-tumor monoclonal antibody KS1/4, labeled with four different radionuclides, in athymic (nu/nu) mice bearing human lung adenocarcinoma. Several radiolabeling methods were used: the first involved coupling a suitable bifunctional chelating agent, such as DTPA, to the KS1/4 monoclonal antibody, followed by binding the radiometal, either 113mIn or 111In. Radioiodination was carried out by the chloramine-T method with 131I, and intrinsic labeling by generating the hybridoma in the presence of 75Se-methionine. An examination of tumors and major organs of mice injected with one of the above radiolabeled KS1/4 MoAbs, and biodistribution at various time intervals up to 96 h post injection revealed that iodination and intrinsic labeling yield the highest tumor uptake. Because of the relatively high deiodination that occurs in vivo, and the high 75Se content in the circulation, the preferential uptake (tumor-to-blood ratio) of these radiopharmaceuticals lags behind the equivalent ratios for the In-labeled MoAb. In the latter group of animals, a second consecutive injection of the labeled MoAb resulted in elevated blood level of radioindium, as well as a corresponding decrease in tumor-to-blood ratios.

Adenocarcinoma↗

First evaluation of technetium-99m dimercaptopropionyl albumin as a possible tracer agent for ventriculography in a volunteer.

Technetium-99m labelled red blood cells (99mTc-RBCs) are the standard radiopharmaceutical for radionuclide ventriculography but suffer from some practical disadvantages such as risk of viral contamination and lengthy preparation (in vitro labelling) or poor labelling efficiency due to patient medication interactions (in vivo labelling). 99mTc-labelled human serum albumin (HSA) is not really a valuable alternative as the activity diffuses too rapidly out of the vascular space due to the weak binding of the radionuclide. We have modified HSA by reaction with N-hydroxysuccinimidyl 2,3-di(S-acetylmercapto)propionate (SAMP) to introduce a varying number of 2,3-dimercaptopropionyl (DMP) side chains. The resulting DMP-HSA can be rapidly labelled with 99mTc at room temperature by simple addition of stannous ions and eluate of a 99mTc generator. After evaluation in mice and rabbits, two different 99mTc-DMP-HSA preparations - obtained after reaction of SAMP with albumin in a molar ratio of, respectively, 8:1 and 16:1 - were tested in a volunteer and compared to 99mTc-RBCs. The blood time-activity curves of the three preparations were quite similar but both 99mTc-DMP-HSA preparations were excreted much less into the urine than 99mTc-RBCs. Ventriculography was performed with the three tracer agents, each time with a 1-week interval. In the three studies, the heart was clearly visualized and the left and right ventricle could be easily delineated. The ejection fractions obtained after administration of the three preparations were similar. With both 99mTc-DMP-HSA preparations the low activity in the spleen was a distinct advantage and facilitated delineation of the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythrocytes↗

Flow characteristics of soft-tissue vascular anomalies evaluated by direct puncture scintigraphy.

Soft-tissue vascular anomalies such as haemangioma and vascular malformation are treated by surgical resection, arterial embolization or sclerotherapy. Because the effect of sclerotherapy, i.e. the percutaneous injection of sclerosing agents, depends on intralesional haemodynamics, estimation of flow characteristics of soft-tissue vascular anomalies is essential when determining appropriate patient management. However, lesions are at present divided into only two groups: high flow and low flow. We have developed a new method, direct puncture scintigraphy, to evaluate in detail the haemodynamics of vascular anomalies under conditions simulating sclerotherapy. Twenty-six soft-tissue vascular anomalies in 21 patients were studied. After 30 MBq of technetium-99m Sn colloid was injected percutaneously into the intravascular space of the lesion, dynamic imaging was performed for 5 min. A time-activity curve for the lesion was generated, with the infiltrated activity on injection subtracted. A monoexponential curve was fitted to the declining phase of the time-activity curve, and mean vascular transit time (MTT) was obtained. The lesions were classified into high-flow and low-flow lesions based on radionuclide angiography with intravenous injection of 99mTc-labelled red blood cells, and estimates of MTT in the two groups were compared. The imaging procedures were carried out with no major complications, and broad intralesional diffusion of 99mTc-Sn colloid was achieved in most lesions. The high-flow lesions (six lesions) had a short MTT, ranging from 1.6 to 3.4 s, while the low-flow lesions (20 lesions) had a longer MTT, with no overlap between the groups. MTT showed a wide range in low-flow lesions: it was less than 30 s in six lesions and more than 10 min in five other lesions. Direct puncture scintigraphy provides a quantitative indicator of the flow characteristics of soft-tissue vascular anomalies, and may aid in determining treatment strategies for patients with vascular anomalies.

Adolescent↗

Nuclear medicine in problems of fertility and impotence.

Nuclear medicine techniques may be used to test fallopian tube patency and penile vascular inflow and outflow. Radionuclide hysterosalpingography (HSP) is a readily performed method of evaluating fallopian tube patency, and is believed to be more physiologic and functionally informative than the accepted radiologic method of contrast HSP. The test is simple to perform and interpret and offers an accurate alternative to the contrast examination. For scintigraphic evaluation of impotence, blood pool studies are most useful in assessing the integrity of arterial inflow, but may also be used to generate indices of venous leak. Washout of xenon after subcutaneous injection, in the flaccid state, has been used as a measure of baseline penile perfusion, as has intracavernosal injections in the flaccid penis. Intracavernosal xenon washout during erection seems the most useful method of testing venous integrity. Washout using technetium-99m (99mTc)-labeled red blood cells (99mTc-RBC) may emerge as a convenient alternative to the more technically difficult xenon examinations.

Erectile Dysfunction↗