Synthesis, optimization and biological evaluation of 99mTc-digoxin as possible cardiac imaging agent.

Heart imaging radiopharmaceuticals could improve the diagnostic value of routine heart scanning for detecting cardiac disorders. The aim of the study was to prepare high radiochemical purity 99mTc-Digoxin in a yield of about 98%. The optimal conditions for labelling were as follows: 100µg of Digoxin, 2µg of SnCl2•2H2O, room temperature (25±1°C), reaction retention time of 30 min at pH 7. Under these conditions, the radiochemical yield of 99mTc-Digoxin reaches 98%. In vivo bio distribution was performed in normal Swiss Albino mice at different time intervals after administration of 99mTc-Digoxin.Scintigraphic study of 99mTc-Digoxin was performed in rabbits. The heart uptake of 99mTc-Digoxin was sufficiently high and thus may be a potential myocardial imaging radiopharmaceutical applicable in cardiology.

Utility of Tc-99m MDP bone SPECT in evaluation of osseous involvement in craniofacial malignancies.

PURPOSE: To assess the role of technetium-99m methoxy diphosphonate (Tc-99m MDP) single photon emission tomography (SPECT) imaging for the detection of osseous invasion in craniofacial malignancies. MATERIAL AND METHODS: The study was performed in 45 subjects using Tc-99m MDP (740 MBq). Out of 45 subjects, 30 were patients had different craniofacial malignancies, and 15 subjects who did not have any malignancy served as controls. Planar imaging was performed. Anterior, lateral and oblique lateral views of the skull were obtained. SPECT imaging was done taking 64 views of the skull in a 360 ° circular path, each 40 s with 128 × 128 matrices. Scans were visually interpreted using a score of 0, 1, and 2, representing a lesion as definitely absent, doubtful, and definitely present, respectively. Planar scans were compared with the SPECT images. RESULTS: Bone SPECT detected more lesions as compared to planar bone scan and plain radiographs. SPECT was found to be superior to planar imaging and radiographs in the detection and efficient demonstration of the extent of osseous invasion of craniofacial cancer. Sensitivity was 100% for SPECT and 83.33% for planar bone scan. CONCLUSION: SPECT imaging of the skull is a very beneficial complementary form of investigation in patients with craniofacial malignancies for the assessment of osseous invasion, particularly in tumors likely to invade the skull base.

Prevalence of diabetes and its correlates in urban population of Pakistan: A Cross-sectional survey.

OBJECTIVE: To determine the prevalence of diabetes mellitus and its associated risk factors in urban population. METHODS: The cross-sectional study was carried out at four union councils of Rawalpindi, Pakistan, from May to September 2014, and comprised members of the general public.A questionnaire was administered to obtain information about demographic characteristics and risk factors. Anthropometric and blood pressure measurements were obtained from the participants. Venous blood samples were taken for measuring glycated haemoglobin. SPSS 20 was used for data analysis. RESULTS: Of the 404 participants, 181(44.8%) were men and 223(55.2%) were women. The overall mean age was 42.3±13 years. Overall prevalence of diabetes was 133(32.9%) and that of pre-diabetes was 151(37.4%). The prevalence of diabetes was 203(50.3%) in 50-65 years age group and 143(35.4%) among obese subjects. Diabetes was significantly associated with increasing age (35-49 years (p<0.05); 50-65 years (p<0.01), positive parental (p<0.05) and sibling (p<0.05) history of diabetes, hypertension (p<0.01) and central obesity (p<0.05). CONCLUSIONS: The prevalence of diabetes and pre-diabetes was very high. Prevalence increased with increasing age and body mass index. Major independent risk factors were increasing age, central obesity, and family history of diabetes and hypertension.

Comparison of gamma camera-based methods to measure glomerular filtration rate in potential kidney donors.

INTRODUCTION: The aim of this study was to compare two gamma camera-based methods (Gates' method and Inoue's method) for measuring glomerular filtration rate (GFR) with Russell's two plasma sample clearance method (2-PSC), which was taken as the gold standard. MATERIALS AND METHODS: In 94 healthy potential kidney donors (25 women and 69 men), GFR was measured by means of the 2-PSC method and was compared with Gates' and Inoue's methods of assessing GFR after technetium-99m-labeled diethylene triamine penta-acetic acid (99 mTc-DTPA) injection. RESULTS: Inoue's method showed no statistically significant difference (P=0.22) with the gold standard (2-PSC); there was good correlation (r=0.69) and least bias (-1.91 ml/min/1.73 m², root mean squared error=11.85 ml/min/1.73 m²). Gates' method showed weak correlation (r=0.36) and tended to underestimate GFR by 21% with bias of 25 ml/min/1.73 m² and root mean squared error of 29.97. CONCLUSION: For a normal healthy adult population, Inoue's method gives a better measure of GFR in contrast to Gates' method when compared with 2-PSC method of GFR calculation.

Formulation and evaluation of a single vial lyophilized preparation of technetium-99m labeled ethylene dicysteine as a renal scintigraphic agent.

(99m)Tc labeled N-N-ethylene-L, L-dicysteine (EC) was introduced in form of multiple-step kit as an alternate renal imaging radiopharmaceutical for commonly used (99m)Tc-MAG3. We developed a single component lyophilized kit of EC ready to be labeled with (99m)Tc. We present the optimization of the components of our formulation, its evaluation in animal models, normal human volunteers and patients of various renal diseases, in comparison with (99m)Tc-MAG3. Efficient labeling of EC was achieved with our preparation at pH 7 to 12. The formulation at pH 8 was used further for bio distribution studies in organs of sacrificed Sprague Dawley rats and a live rhesus monkey using scintigraphy. After satisfactory bio-distribution results, the kit was then evaluated in normal human volunteers through renography. But the renogram parameters of (99m)Tc-EC (pH 8) were statistically inferior to (99m)Tc-MAG3. Surrogate kit at pH 10 was therefore developed and re-evaluated in rats for organ bio distribution. After favorable results the kit was then assessed further in normal volunteers and a group of patients with various renal disorders via scintigraphy. The EC kit developed at pH 10 gave images better than and scintigraphic parameters comparable to (99m)Tc-MAG3. It was concluded that single vial kit we formulated easy to prepare than three-vial kit and can be used as an alternate to (99m)Tc-MAG3.

A comparison of single plasma sample methods to estimate renal clearance using 99mTc-ethylenedicysteine and 99mTc-mercaptoacetyltriglycine.

Several single sample methods for determination of (99m)Tc-mercaptoacetyltriglycine (MAG3) clearance are being used clinically. Kabasakal et al. proposed a similar formula for (99m)Tc-ethylenedicysteine (EC). This study was performed to compare his method with Bubeck et al. formula for (99m)Tc-MAG3 already in use. Twenty-eight subjects divided in two groups were registered which included 22 patients with various renal diseases (group-I) and six normal volunteers (group II). All subjects were studied twice using both the radiopharmaceuticals. The images and renogram parameters, that is TMAX and T1/2 of both the agents, were similar in all the subjects. The clearance of the (99m)Tc-EC was however considerably higher than (99m)Tc-MAG3 in both the groups (mean ± SEM =279 ± 14 ml min(-1)/1.73 m(2) versus 177 ± 15 ml min(-1)/1.73 m(2) in group-I and 377 ± 11.90 ml min(-1)/1.73 m(2) versus 238 ± 8.23 ml min(-1)/1.73 m(2) in group II). This difference was more pronounced in cases with reduced renal functions. Among the Effective Renal Plasma Flow (ERPF) values determined from EC and MAG3 clearances in six normal volunteers, four cases only in MAG3 had ERPF below the lower limit. This study has demonstrated superiority of single sample method for (99 m)Tc-EC clearance over its analogous method for (99m)Tc-MAG3.

Utility of 99mTc-labelled antimicrobial peptide ubiquicidin (29-41) in the diagnosis of diabetic foot infection.

PURPOSE: Detection of osteomyelitis beneath a diabetic foot ulcer is imperative for proper management; however, accurate and noninvasive diagnosis of osteomyelitis remains a challenge. Ubiquicidin 29-41 (UBI 29-41) is a synthetic antimicrobial peptide fragment reported to be highly infection-specific. (99m)Tc-UBI 29-41 has recently been reported to be a promising radiotracer for infection imaging. The aim of this prospective study was to evaluate the utility of (99m)Tc-UBI 29-41 scintigraphy in diabetic patients with suspected osteomyelitis of the foot. METHODS: Included in the study were 65 patients with type 2 diabetes mellitus and foot ulcer and with clinical suspicion of osteomyelitis . Each patient had a three-phase bone scan and a (99m)Tc-UBI scan at 30 and 60 min after injection. The scan was considered to be consistent with osteomyelitis when the (99m)Tc-UBI 29-41 uptake was concordant with the (99m)Tc-MDP uptake. It was considered negative for osteomyelitis if there was no uptake of (99m)Tc-UBI 29-41 or if (99m)Tc-UBI 29-41 accumulated in an area not concordant with the abnormal uptake of (99m)Tc-MDP on the bone scan. In the latter case a diagnosis of soft-tissue infection was made. Bone infection was confirmed by bone biopsy/culture and by clinical and radiological follow-up. RESULTS: Final analysis was done in 55 patients. Osteomyelitis was confirmed in 37 patients, and 18 patients were free of bone infection. (99m)Tc-UBI 29-41 was positive in all 37 patients and with the bone scan as the reference for the bone identified all osteomyelitic foci (68 in total). (99m)Tc-UBI 29-41 was negative for osteomyelitis in all 18 patients, and 17 of these patients were diagnosed with soft-tissue infection ((99m)Tc-UBI 29-41 accumulation without concordant abnormal uptake on bone scintigraphy). The sensitivity, specificity and accuracy of (99m)Tc-UBI 29-41 scan in combination with three-phase bone scan for the diagnosis of osteomyelitis in diabetic foot was 100 %. Accuracy for soft-tissue infection was also 100 %. Maximum accumulation of the (99m)Tc-UBI 29-41 with maximum target to background activity was observed in the infectious foci at 30 min after injection. CONCLUSION: Tc-UBI 29-41 may be a useful agent for the accurate diagnosis of bone infection in diabetic foot because of the high accuracy demonstrated in this pilot study. It was able to differentiate between bone and soft-tissue involvement effectively in combination with a bone scan.

Role of Tc99m MIBI SPECT in the assessment of treatment response in pharyngeal carcinoma.

The purpose of this study was to compare Tc(99m) MIBI SPECT imaging with computed tomography (CT) for assessment of post-radiotherapy treatment response in pharyngeal carcinoma. Twenty-two subjects took part in this study, which included six patients with nasopharyngeal carcinoma (Group I), three patients with oropharyngeal carcinoma and eight patients with hypopharyngeal carcinoma (Group II), and five control patients (Group III). All scans were analyzed qualitatively and quantitatively and correlated with findings on local examination and biopsy. Various indices such as ratios of nasopharynx, oropharynx, and hypopharynx to scalp (NSR, OSR, HSR), to nuchal muscles (NNR, ONR, HNR), and parotid glands (NPR, OPR, HPR) were calculated. The mean values of these above mentioned ratios calculated in the control group (Group III) were used as cutoff values to determine the presence or absence of tumor tissue in the patient groups (Groups I and II). The cutoff values calculated were 2.89 (NSR), 1.39 (NNR), 0.57(NPR), 3.83 (OSR), 1.81 (ONR), 0.83 (OPR), 2.86 (HSR), 1.73 (HNR), and 0.59 (HPR). The results revealed 100% sensitivity for primary nasopharyngeal tumors but less sensitivity for primary oropharyngeal and hypopharyngeal tumors (63.6%). Based on a relative decrease in tracer uptake, Tc(99m) MIBI SPECT scan was able to predict partial remission, complete remission, and no response on post-therapy scans. There were three false-negative results of disease progression in addition to evidence of disease eradication on CT scan. Thus Tc(99m) MIBI SPECT imaging has shown promising results in the detection of primary tumors and evaluation of treatment response much earlier than CT scan, which needs further exploration and large-scale studies.

Inhibition of tryptophan pyrrolase activity in restraint female rats following medroxyprogesterone administration.

OBJECTIVE: To determine the effects of Medroxyprogesterone (hormonal contraceptive) in restraint stressed female rats in relation to tryptophan metabolism. DESIGN: Pre-clinical study. PLACE AND DURATION OF STUDY: Department of Biochemistry, University of Karachi. The investigation was carried out in the year 2003. MATERIALS AND METHODS: Female Albino Wistar rats (150-200 gm body wt) were selected and divided into four groups (n=5 in each group). Rats were injected intraperitoneally either vehicle or Medroxyprogesterone (25mg/kg/ml) and were immediately subjected to 2 hours restraint stress while respective controls remained in their home cages. RESULTS: In restraint stress group, hepatic holo and total tryptophan pyrrolase activities were increased. Liver tryptophan, total serum tryptophan and albumin concentration were decreased. Brain tryptophan, 5HT and 5HIAA concentrations were increased. Medroxyprogesterone administration in unrestraint rats inhibited holo, total and apo enzyme activities with increases in liver tryptophan concentrations. Effect of restraint stress following Medroxyprogesterone administration when compared with drug injected unrestrained group showed increase in holo and total tryptophan pyrrolase activities with decrease in liver tryptophan concentrations. Brain tryptophan, 5HT and 5HIAA levels were increased. Results when compared with vehicle injected stressed-rats showed that total and apo tryptophan pyrrolase activities were decreased. Liver tryptophan, serum tryptophan and albumin concentrations were increased but brain tryptophan metabolism was not effected. CONCLUSION: It is concluded that Medroxyprogesterone inhibits stress induce increases in peripheral tryptophan metabolism and increases plasma tryptophan. Although stress induced increases in brain indoles were not effected by the drug at two hours, further studies on time course effects of this drug will be needed to explore its possible anxiolytic effects.

Localizing hyperfunctioning parathyroid tissue: MRI or nuclear study or both?

The surgical approach to primary hyperparathyroidism patients has changed recently with minimally invasive surgery becoming more common. This retrospective study reviews the relative sensitivities of dual-phase sestamibi (DP-SI) and magnetic resonance imaging (MRI) in preoperative patients. We found that MRI was more sensitive, but the difference was not statistically significant. Magnetic resonance imaging enhanced the ability to localize abnormal tissues when the DP-SI was negative. Together, both tests demonstrated a sensitivity of 92%. We recommend performing DP-SI initially, and if negative, MRI. This should provide the highest imaging sensitivity at the lowest cost.