Re-utilization of long lived 99Tc radio isotope via Photon induced nuclear reactions.

Technetium-99 is a radioactive waste produced primarily in nuclear reactors. It is also left as radioactive waste in hospitals, directly from 99mTc isomeric state. To bring down the quantity of technetium-99 radioactive waste, the nuclear reactions using photon beam is explored. The integral cross section of the reaction 99Tc(γ,γ')99mTc has been determined using the photo-nuclear activation method. The experiment was done using bremsstrahlung photons having endpoint energies viz. 6, 9, 12, 16, and 20 MeV. 115In(γ,γ')115mIn reaction has been used as a monitor reaction, for the flux normalization of the bremsstrahlung spectrum. Theoretical model calculations have been done using the nuclear reaction code Talys 1.9. Theoretical parameter values are optimized with the presently obtained data. Total cross sections are estimated and investigated the feasibility of re-utilization of the technetium-99 radioactive isotope.

Reactor produced [64Cu]CuCl2 as a PET radiopharmaceutical for cancer imaging: from radiochemistry laboratory to nuclear medicine clinic.

OBJECTIVE: Copper-64 is a useful theranostic radioisotope that is attracting renewed interest from the nuclear medicine community in the recent times. This study aims to demonstrate the utility of research reactors to produce clinical-grade 64Cu via 63Cu(n,γ)64Cu reaction and use it in the form of [64Cu]CuCl2 as a radiopharmaceutical for PET imaging of cancer in human patients. METHODS: Copper-64 was produced by irradiation of natural CuO target in a medium flux research reactor. The irradiated target was radiochemically processed and detailed quality control analyses were carried out. Sub-acute toxicity studies were carried out with different doses of Cu in Wistar rats. The biological efficacy of the radiopharmaceutical was established in preclinical setting by biodistribution studies in melanoma tumor bearing mice. After getting regulatory approvals, [64Cu]CuCl2 formulation was clinically used for PET imaging of prostate cancer and glioblastoma patients. RESULTS: Large-scale (~ 30 GBq) production of 64Cu could be achieved in a typical batch and it was adequate for formulation of clinical doses for multiple patients. The radiopharmaceutical met all the purity requirements for administration in human subjects. Studies carried out in animal model showed that the toxicity due to "cold" Cu in clinical dose of [64Cu]CuCl2 for PET scans would be negligible. Clinical PET scans showed satisfactory uptake of the radiopharmaceutical in the primary cancer and its metastatic sites. CONCLUSIONS: To the best of our knowledge, this is the first study on use of reactor produced [64Cu]CuCl2 for PET imaging of cancer in human patients. It is envisaged that this route of production of 64Cu would aid towards affordable availability of this radioisotope for widespread clinical use in countries with limited cyclotron facilities.

A simple and robust method for radiochemical separation of no-carrier-added 64Cu produced in a research reactor for radiopharmaceutical preparation.

Copper-64 is an excellent theranostic radiometal that is gaining renewed attention of the clinical community in the recent times. In order to meet the increasing demand of this radiometal, we have demonstrated the viability of its production via 64Zn (n,p) 64Cu reaction in a nuclear reactor. A semi-automated radiochemical separation module based on selective extraction of 64Cu as dithizonate complex was developed. The maximum available activity at the end of irradiation was ~ 700 MBq. The overall yield of 64Cu after the separation process was >85% and it could be obtained with ~12 GBq/µg specific activity, >99.9% radionuclidic purity and >98% radiochemical purity. The separated 64Cu could be utilized for preparation of a wide variety of radiopharmaceuticals.

A facile method for electrochemical separation of 181-186Re from proton irradiated natural tungsten oxide target.

Routine availability of high specific activity 186Re would provide a significant boost to the development of potent theranostic radiopharmaceuticals. In the present study, 181-186Re was produced by proton bombardment (12 MeV, average beam intensity 180 nΑ) for 60 h on natural tungsten oxide target. A facile electrochemical method has been developed for radiochemical separation of Re radioisotopes from irradiated target material. The overall yield of the process was >80% and Re radioisotopes could be separated in a form suitable for preparation of radiopharmaceuticals.

Production of gaseous radiotracers for industrial applications.

This paper describes prerequisite tests, analysis and the procedure for irradiation of gaseous targets and production of gaseous radioisotopes i.e. argon-41 ((41)Ar) and krypton-79 ((79)Kr) in a 100MWTh DHRUVA reactor located at Bhabha Atomic Research Center (BARC), Trombay, Mumbai, India. The produced radioisotopes will be used as radiotracers for tracing gas phase in industrial process systems. Various details and prequalification tests required for irradiation of gaseous targets are discussed. The procedure for regular production of (41)Ar and (79)Kr, and assay of their activity were standardized. Theoretically estimated and experimentally produced amounts of activities of the two radioisotopes, irradiated at identical conditions, were compared and found to be in good agreement. Based on the various tests, radiological safety analysis and standardization of the irradiation procedure, necessary approval was obtained from the competent reactor operating and safety authorities for regular production of gaseous radiotracers in DHRUVA reactor.

Studies on the development of ¹69Yb-brachytherapy seeds: New generation brachytherapy sources for the management of cancer.

This paper describes development of (169)Yb-seeds by encapsulating 0.6-0.65 mm (ϕ) sized (169)Yb2O3 microspheres in titanium capsules. Microspheres synthesized by a sol-gel route were characterized by XRD, SEM/EDS and ICP-AES. Optimization of neutron irradiation was accomplished and (169)Yb-seeds up to 74 MBq of (169)Yb could be produced from natural Yb2O3 microspheres, which have the potential for use in prostate brachytherapy. A protocol to prepare (169)Yb-brachytherapy sources (2.96-3.7 TBq of (169)Yb) with the use of enriched targets was also formulated.

Practicality of production of ³²P by direct neutron activation for its utilization in bone pain palliation as Na3[³²P]PO4.

Large-scale production of ³²P for its clinical use in palliative care of painful bone metastasis in the form of Na3[³²P]PO4 (³²P-sodium orthophosphate) has been practiced for six decades. The classical route of production of ³²P by (n,p) reaction on high purity elemental sulfur yields no-carrier-added (NCA) ³²P. Since high specific activity ³²P is not essential for the formulation of Na3[³²P]PO4 for bone pain palliation, an alternate route of production of ³²P by direct neutron capture using elemental phosphorus target [(31)P(n,γ)³²P] was envisaged and its suitability for use in bone pain palliation was evaluated. Toward this, irradiation of elemental red phosphorus target was carried out at a neutron flux of 8×10¹³ n/cm².s for 60 days and this yielded ³²P with a specific activity of 230±15 MBq/mg (6.2±0.4 mCi/mg) having >99.9% radionuclidic purity. About 370-555 MBq (10-15 mCi) doses of Na3[³²P]PO4 were formulated in sterile saline (pH 7.4) using the ³²P produced. The radiochemical purity of the formulation was found to be ~99% with respect to PO4³â». The formulation exhibited good in vitro stability in saline and in human serum. Biodistribution studies carried out in normal Wistar rats revealed comparable pharmacokinetic properties of the formulation prepared using (n,γ) produced ³²P with that of NCA ³²P produced by (n,p) route. Besides having the advantages of simplicity in radiochemical processing and minimum radioactive waste generation, use of the proposed production route in place of the traditional ³²S(n,p)³²P route would result in better utilization of irradiation volume of research reactors.

Infrared thermal imaging for detection of peripheral vascular disorders.

Body temperature is a very useful parameter for diagnosing diseases. There is a definite correlation between body temperature and diseases. We have used Infrared Thermography to study noninvasive diagnosis of peripheral vascular diseases. Temperature gradients are observed in the affected regions of patients with vascular disorders, which indicate abnormal blood flow in the affected region. Thermal imaging results are well correlated with the clinical findings. Certain areas on the affected limbs show increased temperature profiles, probably due to inflammation and underlying venous flow changes. In general the temperature contrast in the affected regions is about 0.7 to 1 degrees C above the normal regions, due to sluggish blood circulation. The results suggest that the thermal imaging technique is an effective technique for detecting small temperature changes in the human body due to vascular disorders.

Assessment of bone mineral density by DXA and the trabecular microarchitecture of the calcaneum by texture analysis in pre- and postmenopausal women in the evaluation of osteoporosis.

The in vivo evaluation of trabecular bone structure could be useful in the diagnosis of osteoporosis for the characterization of therapeutic response and understanding the role of parameters other than bone mineral density (BMD) in defining skeletal status. This study was made to evaluate changes taking place in the trabecular architecture of bone with age and menopausal status in women. The findings are compared with the femoral neck bone as well as the trochantar bone mineral density determined by dual energy X-ray absorptiometry (DXA), which is a standard reference test for evaluation of osteoporosis. Seventy females were recruited for the study, 25 premenopausal (mean age ± SD: 39.4 ± 3.8) and 45 postmenopausal (mean age ± SD: 57.9 ± 7.9) women. The right femoral neck bone mineral density was measured for them by dual energy X-ray absorptiometry (DXA). For the same individuals, lateral view radiographs of the right calcaneum were taken as well. The radiographs were digitized and the region of interest (ROI) of 256 × 256 pixels was selected, the run length matrix was computed for calculating seven parameters [Table 1] and the two dimensional fast Fourier transform of the image was calculated. Using the FFT, the power spectral density (PSD) was derived and the root mean square (RMS) value was determined. Our results confirm that age has a significant influence on the texture of the trabecular bone and bone mineral density.

Influence of P. vivax malaria on erythrocyte aggregation and deformability.

Malaria due to Plasmodium vivax affects blood flow in cardiovascular system. The present work is aimed to determine the variability of erythrocyte deformability and aggregation in malaria patients in comparison with that of normal subjects. Blood samples of malaria patients (n=16), selected based on occurrence of parasitaemia, are categorized into low (LP), medium (MP) and high parasitaemia (HP), which represent increasing levels of the disease severity. For measurement of aggregation and deformability, by laser aggregometer and optical hemorheometer, the erythrocyte suspensions are prepared in plasma and physiological saline at hematocrit 5%. The results show that the erythrocyte deformability is significantly reduced (p<0.001) with the increasing level of parasitaemia. Despite this decrease in deformability, the aggregation parameters are significantly increased, indicating the occurrence of hyper-aggregation, particularly in MP and HP, due to involvement of various factors. These changes may partly be contributing in the observed changes in blood flow in the microcirculation.

A multicenter clinical evaluation of the Clot Signature Analyzer.

BACKGROUND: The Clot Signature Analyzer (CSA) was designed to assess global hemostasis as a screening assay using non-anticoagulated whole blood. Three different measurements are produced by the instrument: platelet hemostasis time (PHT), clot time (CT), and collagen-induced thrombus formation (CITF). OBJECTIVES: The purpose of the present study was to determine normal ranges for these measurements and assess the performance of the CSA in patients with well-characterized hemostatic disorders and in normal subjects. PATIENTS AND METHODS: Four institutions participated in the study. Each established their own normal reference ranges. Patients with well-characterized hemostatic disorders and concurrent normal controls were subsequently examined. RESULTS: Normal ranges between institutions were similar although statistically different. One hundred and eight patients were examined: 46 individuals with von Willebrand disease (VWD) (type 1, 26; type 2A, 11; type 2B, six; type 3, three); 38 patients with a coagulation factor deficiency; 13 individuals with platelet function defects; 10 patients taking warfarin; and one individual on low-molecular-weight heparin. Of these patients, 89% had at least one abnormality by CSA: 42/46 VWD patients, 35/38 coagulation protein defect patients, 9/13 patients with platelet function defects, 9/10 patients on warfarin and 1/1 patient on low-molecular-weight heparin. Of 116 normal subjects, 103 (89%) fell within the centers' normal range. These data suggest that the CSA has a good sensitivity for bleeding disorders.

Cell mediated immunity to Plasmodium vivax infection: in vitro inhibition of parasite growth by monocyte derived macrophages.

OBJECTIVE: To study the ability of soluble blood stage or cell associated antigens of Plasmodium vivax to stimulate human peripheral blood mononuclear cells (PBMC) and produce factors capable of causing inhibition of parasite growth in vitro was the objective of this investigation. METHOD: A local isolate of P vivax was either synchronized by triple sorbitol lysis for antigen preparation or used as unsynchronized culture for parasite inhibition, employing a macrophage inhibition assay. The soluble or cell associated antigens of P vivax were added to human monocyte derived macrophages with P vivax parasitized red blood cells. The percent inhibition of parasite growth was examined after 72 hrs by microscopy of Giemsa stained smears of red blood cells from the experimental and control groups. RESULTS: The differences in parasite inhibition were compared using Wilcoxon rank sum test for paired differences. Unstimulated PBMC supernatants did not inhibit parasite growth. Significant inhibition of parasite growth (90%) was seen after incubating P vivax infected erythrocytes with PBMC supernatants resulting from stimulation with soluble antigens (T = 3; P < 0.05). However, the cell associated antigens of P vivax did not stimulate PBMC to activate macrophages for parasite killing in vitro (T = 14, P < 0.05). CONCLUSION: We conclude that the soluble blood stage antigens of P vivax can stimulate human PBMC to produce factors capable of activating macrophages to function as effector cells in P vivax malaria.

Detection of Mycobacterium tuberculosis by polymerase chain reaction in 301 biological samples--a comparative study.

A repetitive target sequences of Mycobacterium tuberculosis DNA was amplified by polymerase chain reaction (PCR) in a total of 301 clinical samples. Sputum, blood, pleural fluid, and bronchial lavage specimen were taken from clinically suspected causes of tuberculosis and processed for the diagnosis of tuberculosis using a simplified procedure of DNA extraction. PCR was positive in a total of 58 samples (58/301--19.3%). A significant number of smear and culture negative cases of tuberculosis were PCR positive (37/174--21.26%). This finding, combined with the absence of either false positive or false negative results reflects the greater usefulness of this technique.

A retrospective study of 1247 cases of intracranial tuberculomata diagnosed by computerized tomography.

Tuberculomata in the brain are a common feature of intracranial tuberculosis, especially in the sub-continent. With the advent of computerized tomography, a diagnosis can be made, in many instances. In this study, 1247 cases of CT diagnosed intracranial tuberculomata were analysed retrospectively with regard to the age, sex and symptoms of the patient as well as the number, site and distribution of the lesion within the brain. Tabulation with respect to age revealed that patients with ages ranging from 1-30 years accounted for 60% of the cases. The male to female ratio was approximately 60:40. The parietal hemisphere accounted for 46.75% of the cases. Left sided lesion were more common when compared with the right (statistically significant). We postulate that this increased occurrence of left sided lesions is due to the hematogenous mode of infection and increased blood flow to the dominant hemisphere.

Right ventricular mural infective endocarditis in a patient with burns.

An individual who had sustained 43% burns and then developed blood culture negative right ventricular infective endocarditis and right basal segmental pulmonary infarction is reported. Echocardiography detected vegetations in the mid right ventricle. The patient had a central venous catheter in situ during the initial stage of management of burns. Following therapy, he recovered uneventfully from his extremely toxic and febrile state.

Acute abdomen in a patient treated with lamprene.

Patients receiving Lamprene may develop acute abdominal symptoms which simulate an abdominal emergency. Withdrawal of the drug relieves these symptoms. The absorption of Lamprene can be increased and deposition in the reticuloendothelial system as crystals can be avoided if it is administered in an alcoholic medium.