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Biomedical subjects

U P Chauhan

Publications and source records attributed to U P Chauhan.

At least 19 recordsLinked to original sources

Evaluation of (99m)Tc-labeled photosan-3, a hematoporphyrin derivative, as a potential radiopharmaceutical for tumor scintigraphy.

A quick and reproducible method for radiolabeling of Photosan-3(R), a photosensitizer used worldwide for photodynamic therapy (PDT) of cancer, with radioisotope of technetium ((99m)Tc) was developed. The radiotracer was evaluated for radiochemical purity, stability, and tissue distribution in a murine tumor model. The (99m)Tc-Photosan-3, which was prepared by using (99m)Tc-pertechnetate in place of reduced (99m)Tc, demonstrated better labeling efficiency (>90%) and reproducibility. The procedure also minimized radiation exposure to the radiochemist because handling time was considerably reduced. Due to the commercial availability of Photosan-3, the risk of batch-to-batch variation in the in situ synthesis of hematoporphyrin derivative, which is a complex mixture of at least five compounds, was also significantly reduced. The biodistribution studies and tumor scintigraphy confirmed that (99m)Tc-labeled Photosan-3 was preferentially taken up by the neoplastic tissue similar to the parent compound. In addition to its applications in tumor imaging, (99m)Tc-Photosan-3 could also be used for estimating tumor uptake of Photosan-3 as may be required for individualization of clinical protocols of PDT.

Animals↗

Evaluation of (99m)Tc-labeled photosan-3, a hematoporphyrin derivative, as a potential radiopharmaceutical for tumor scintigraphy.

A quick and reproducible method for radiolabeling of Photosan-3(R), a photosensitizer used worldwide for photodynamic therapy (PDT) of cancer, with radioisotope of technetium ((99m)Tc) was developed. The radiotracer was evaluated for radiochemical purity, stability, and finally tissue distribution in a murine tumor model. The (99m)Tc-Photosan-3 prepared by using (99m)Tc-pertechnetate in place of reduced (99m)Tc demonstrated better labeling efficiency (>90%) and reproducibility. The procedure also minimized the radiation exposure to the radiochemist as handling time was considerably reduced. Due to the commercial availability of Photosan-3, the risk of batch-to-batch variation in the in situ synthesis of hematoporphyrin derivative, which is a complex mixture of at least five compounds, was also significantly reduced. The biodistribution studies and tumor scintigraphy confirmed that (99m)Tc-labeled Photosan-3 was preferentially taken up by the neoplastic tissue in a manner similar to the parent compound. In addition to applications in tumor imaging, (99m)Tc-Photosan-3 could also be used for estimating tumor uptake of Photosan-3 as may be required for individualization of clinical protocols of PDT.

Animals↗

Scintiscan demonstration of localized bowel loop inflammation. Comparison of Tc-99m dextran, Tc-99m citrate, and Tc-99m human immunoglobulin G.

A 60-year-old man with localized small bowel inflammation underwent abdominal scintigraphy with Tc-99m human polyclonal immunoglobulin G and two experimental inflammation-seeking agents, Tc-99m dextran and Tc-99m citrate. The abnormal loop was visualized in all the three studies. Additionally, the Tc-99m dextran study revealed exudation and luminal transit of the tracer suggestive of regional protein-losing enteropathy. The authors conclude that Tc-99 dextran and Tc-99 citrate are clinically suitable inflammation-seeking agents that need further evaluation, especially for locating abdominal inflammations.

Citrates↗

Scintigraphic diagnosis of gastrointestinal bleeding with 99Tcm-dextran.

Intravenously administered dextran is used clinically as a plasma expander. The aim of this study was to assess the use of 99Tcm-dextran in the diagnosis of gastrointestinal (GI) blood leaks. Twenty-one patients with GI blood loss underwent 99Tcm-dextran scintigraphy, 17 of whom were found to be positive. Pathologic or 99Tcm-RBC (red blood cell) blood pool correlation was possible in 15 cases, while 2 were unconfirmed. No case had a positive 99Tcm-RBC blood pool study and a negative 99Tcm-dextran study. Images obtained with 99Tcm-dextran were generally better than those with 99Tcm-RBC. This agent may have several other advantages over 99Tcm-RBC blood pool and 99Tcm-sulphur colloid scintigraphy for detecting GI blood loss.

Adult↗

A kit for the instant preparation of 99Tcm-citrate for tumour and inflammation scintigraphy.

A lyophilized kit has been developed to produce 99Tcm-citrate (99%) instantly when mixed with 99TcmO4-. The ingredients of the kit, citrate and stannous chloride, are in a ratio of 100:1 (w/w) and are bound to 700 MBq 99Tcm, sufficient for use in a single patient. The shelf life of the kit when kept refrigerated is at least 3 months. The blood clearance and organ distribution of 99Tcm-citrate have been studied in rabbits and mice respectively, showing its fast clearance (55% at 5 min) and low uptake by the reticulo-endothelial system and other organs. The main route of clearance is via the kidneys. Scintigraphic studies in experimental mice have demonstrated high levels of accumulation of 99Tcm-citrate in turpentine-induced abscess (target-to-non-target ratio 4.2:1) and EAT implanted tumour in mice (T/NT 5:1) 1 h after its administration. In keeping with these animal studies, low uptake of 99Tcm-citrate by normal organs and fast blood clearance have been demonstrated in human patients with infection and tumour as early as 5 min post-administration. This study documents a new kit developed for the preparation of 99Tcm-citrate suitable for the scintigraphic assessment of abscess, infection and tumour.

Abscess↗

A simplified kit for instant preparation of technetium-99m human immunoglobulin-G for imaging inflammatory foci.

A kit consisting of reduced human immunoglobulins G (hIgG), methylene diphosphonate, stannous chloride and ascorbic acid has been developed to instantly produce technetium-labelled hIgG of greater than 97% purity and suitable for inflammation foci scintigraphy in patients. The shelf life of the kit when stored at 4-7 degrees C was at least 3 months. 99mTc-hIgG prepared from the kit, when incubated at 37 degrees C for 24 h in physiological saline and human serum was found to degrade by only 7.8 and 4.3%, respectively, thereby indicating high stability of the labelled product. Competitive RIA data did not exhibit loss of immunoreactivity of the hIgG due to its reduction. Blood clearance of the radiopharmaceutical in rabbits exhibited a monophasic exponential pattern. Biodistribution in mice showed uptake by liver (4.93%), kidneys (3.07%) and intestines (2.12%) at 4 h which was reduced to 1.99, 2.18 and 1.93%, respectively at 24 h. Radiolabelled hIgG prepared from the kit was found to be quite satisfactory for inflammation scintigraphy in human patients.

Animals↗

A novel method for labelling human immunoglobulin-G with 99Tcm suitable for inflammation scintigraphy.

An amount of 1.0 mg human immunoglobulin G (hIgG) treated with ascorbic acid at a molar ratio of 1:5000 for 16 h at 4-7 degrees C was mixed with 250 micrograms GHA and 5 micrograms stannous chloride dihydrate in normal saline. Radiolabelling of hIgG (> 98%) was achieved instantly when mixed with 99Tcm-pertechnetate. The preparation was sufficiently stable in serum at 37 degrees C. The competitive binding assay and gel electrophoresis of the native and reduced hIgG did not show any measurable loss in immunoreactivity and intactness due to its reduction. There was no significant decrease in the radiolabel of labelled hIgG when incubated with diethylenetriaminepentaacetate (DTPA) (50-fold), in contrast with about 9% loss of the radiolabel by treating it with a similar concentration of cysteine. Blood clearance of labelled hIgG in rabbits was biphasic with about 78 min and 8 h as T1/2 of the fast and slow phases. Biodistribution of the radiotracer in mice at 4 h showed its uptake by liver (10.2%), kidneys (5.39%), intestines (7.33%) and muscles (3.9%), which altered to 5.63, 3.20, 4.03 and 6.73%, respectively, at 24 h. The radiotracer was excreted through both renal and hepatobiliary routes. High accumulation of the radiolabelled hIgG in inflammatory lesions of the patients confirmed the clinical usefulness of the method developed.

Animals↗

A study of hyperinsulinaemia in Indian hypertensive subjects.

Fasting and 2 hours post-prandial serum insulin levels were estimated in 100 hypertensive subjects and 25 matched, healthy controls, by radio-immuno assay (RIA). Seventy four of the 100 hypertensives exhibited fasting hyperinsulinaemia. Post-prandial hyperinsulinaemia was present in 85 hypertensives. None of the healthy individuals demonstrated hyperinsulinaemia. Although, most hyperinsulinaemic patients exhibited an abnormal lipo-protein profile, there was no statistical correlation between absolute values of lipo-protein and insulin.

Chronic Disease↗

Development of a dextran kit for labelling with 99mTc and its evaluation for lymphoscintigraphy.

A cold dextran (molecular weight 60,000-90,000) kit has been developed by a modified procedure to produce instant preparation of 99mTc-dextran suitable for lymphoscintigraphy. The preparation was subjected to various quality control measures. Effect of pH and amount of stannous chloride as a reducing agent on the labelling efficiency using ITLC were studied. The labelled complex was separated from both the reduced pertechnetate and pertechnetate and quantified. In a series of experiments hydrolysed/reduced 99mTc was found to be less than 3.0%, whereas pertechnetate was approx. 1.0%. Biokinetics of the agent in mice and blood clearance and rate of disappearance from the site of intradermal injection of the agent in rabbits were studied. The tagged agent for imaging of the lymphatic system activated by administering Freund's complete adjuvant (FCA)/E. coli in rabbits exhibited its suitability for lymphoscintigraphy.

Animals↗

Evaluation of sterically stabilized liposomes as a vehicle for targeting technetium-99m labelled radiopharmaceuticals.

Sterically stabilized neutral liposomes (multilamellar vesicles) were prepared by sonicating phosphatidylcholine and cholesterol (molar ratio 4:1) film in phosphate buffered saline (50 mM, pH 7.4) containing 4% Tween 20. Tc-99m-GHA was incorporated in these liposomes by treating 0.5 ml of the suspension with lyophilized GHA kit (5 mg GHA and 250 micrograms SnCl2 x 2 H2O) followed by addition of 1 ml 99mTcO4- (1-3 mCi). The labelling yield was 60-70%. Tween 20 has provided significant stability of the radiolabel as compared to that without its addition, when radiolabelled liposomes were incubated in serum up to 24 h. With respect to Tc-99m-GHA alone, radiolabelled liposomes exhibited 4- to 6-fold greater radioactivity in the blood of rabbits (15 min-24 h). Comparison of biodistribution data of radiolabelled liposomes and Tc-99m-GHA in mice demonstrated a 10- to 12-fold greater hepatic accumulation of radiolabelled liposomes with respect to that of Tc-99m-GHA throughout the period of study (15 min-24 h), though their concentration in the kidneys was comparable.

Animals↗

Evaluation of a DMSA kit for instant preparation of 99mTc(V)-DMSA for tumour and metastasis scintigraphy.

A kit has been developed to instantly prepare 99mTc(V)-DMSA. The freeze-dried kit consisting of DMSA, stannous chloride and ascorbic acid in appropriate proportions, produces quality 99mTc(V)-DMSA when mixed with 0.2 mL of 3.5% NaHCO3 solution and 2-4 mL of (99mTc)pertechnetate. The radiopharmaceutical characterized by chromatography with ITLC-SG in 0.9% saline and horizontal paper electrophoresis in 50 mM vernol buffer, pH 8.6, at a potential gradient of 15 V/cm showed a different mobility with respect to 99mTc(III)-DMSA, a known agent for kidney imaging. The new agent exhibited less plasma protein binding compared to that of 99mTc(III)-DMSA. Biodistribution of the pentavalent DMSA in mouse demonstrated greater uptake in bone and muscle and lower uptake in liver and kidney with respect to trivalent DMSA. The soft tissue tumour specificity and its suitability for tumour scintigraphy was apparent from the scintigrams of mammary carcinoma in a C3H Jax mouse and medullary carcinoma in a patient. Brain metastatic lesions were also visible in a breast carcinoma patient after administering him with the agent.

Animals↗

Tc-99m(V) DMSA imaging. A new approach to studying metastases from breast carcinoma.

Combined Tc-99m MDP skeletal imaging and Tc-99m(V) DMSA whole body scans to detect metastases were performed during the follow-up of 30 patients who underwent surgery for breast carcinoma. Eight patients had normal Tc-99m MDP and Tc-99m(V) DMSA scans and were declared free of metastatic disease, further confirmed by no change in symptomatology over a 1-year follow-up period. Twenty-two patients had positive Tc-99m MDP scans with varied skeletal involvement. Tc-99m(V) DMSA scans showed matched areas of increased radiotracer concentration in bony metastases in 20 of these patients. Tc-99m(V) DMSA concentration was not seen in traumatic vertebral collapse or in coexistent osteoarthritic disease in vertebral metastatic involvement. Interestingly, Tc-99m(V) DMSA showed increased concentration in brain and liver metastases. Pentavalent Tc-99m(V) DMSA appears useful for detecting skeletal and soft-tissue metastases in breast carcinoma, and can improve the specificity of Tc-99m MDP bone scans in screening for bone metastases.

Adult↗

Etiologic significance of mosquito (Anopheles stephensi) in respiratory allergy in India.

The etiologic significance of Anopheles stephensi, a common mosquito species in Delhi, in respiratory allergic disorders was investigated. Intradermal (ID) tests with the mosquito whole body extract (WBE) were performed on 247 patients with bronchial asthma and/or rhinitis and 50 healthy nonallergic volunteers. Of these 247 patients, 118 (47.8%) had positive (1+ to 4+) reactions including 72 (29.1%) with markedly positive (2+ to 4+) ID reactions. We did not observe any 2+ to 4+ skin reactions in normal healthy volunteers, giving evidence for the specificity of markedly positive ID response. The skin test positivity was not influenced by various clinical characteristics (age at onset, duration and type of disease, and family history) of patients included in the study. The specificity of positive ID response was further supported by the results of mosquito RAST with the sera of 14 patients. Ten of the 12 sera (83%) from patients with positive ID response to mosquito WBE were RAST positive. Sera from two patients with negative ID reactions were RAST negative. The bronchial provocation tests (BPTs) were uniformly negative in all five healthy volunteers and two patients showing negative ID responses to mosquito WBE, while the three patients showing 2+ to 4+ responses gave positive BPTs. Our results suggest that mosquito-derived particles are important inhalant allergens in the etiology of IgE-mediated respiratory allergic disorders in India.

Adolescent↗

99mTc-labelled trimethylmonoiodo-IDA: a new radiopharmaceutical for hepatobiliary imaging.

A new radiopharmaceutical, 99mTc-3-iodo-2,4,6-trimethylphenylcarbamoylmethyl iminodiacetic acid (99mTc-trimethylmonoiodo-IDA) was prepared and evaluated for hepatobiliary scintigraphy. The new agent has less plasma protein binding capacity and greater lipophilicity as compared to that of di-isopropyl-IDA. Hepatobiliary specificity, a short transit time and a high gall bladder-to-liver ratio of the new agent were evident from tissue distribution data in mice. Blood tmax and clearance t1/2 of the radiopharmaceutical were observed at 2 and 3.5 min respectively. The hepatic peak-time tmax (5 min) and release time t1/2 (12.75 min) and release t1/2 (25.00 min) suggest the suitability of this agent for hepatobiliary imaging. Results of hepatobiliary scintigraphy in rabbits have further confirmed the above view.

Animals↗

Shared and specific allergenic and antigenic components in the two sexes of American cockroach--Periplaneta americana.

The whole body extracts (WBEs) of female and male cockroaches (Periplaneta americana; Pa) were prepared separately to study the specific and/or shared allergenic and antigenic components in the two sexes. These two extracts were skin-tested on 170 respiratory allergy patients and 52 (30.6%) of them elicited a markedly positive cutaneous reaction (2+ to 4+) to any one or both the WBEs. Of these 52 patients, 32 (61.5%) produced a 2+ to 4+ response to only one, and the remaining 20 (38.5%) to both the extracts. In female and male RASTs to Pa both the extracts produced dose-related inhibition. Using rabbit anti-Pa female serum: (1) immuno-diffusion experiments resulted in lines of identity with the two extracts, and (2) the two-dimensional immunoelectrophoresis of Pa female and Pa male WBEs elicited 12 and nine precipitin peaks, respectively. In partial purification studies, only fraction Pa(F)III (approximately 50 kD) of Pa female WBE and Pa(M)I (greater than or equal to 600 kD) and Pa(M)III (approximately 50 kD) fractions of Pa male WBE revealed significant allergen activity both on skin testing and also in RAST inhibition studies. These results provide evidence for the presence of shared as well as specific allergenic and antigenic components in the two sexes of American cockroach.

Allergens↗