Iranian Journal of Nuclear Medicine
Volume:18 Issue: 2, Summer-Autumn 2010

In this research, [166Ho]Holmium chitosan complex production is described in details, followed by determination of complex radiochemical purity, stability and biodistribution (after intra-articular injection) in wild-type male rats. Finally a Ho-166 based chitosan kit for ultimate radiosynovectomy as well as radiotherapy applications was developed. 166Ho-chitosan complex was prepared using chitosan concentrations and 166HoCl3 followed by intra-articular injection and biodistribution studies in wild-type rats including and excluding injected knee. The [166Ho]Holmium chitosan complex was prepared with high radiochemical yield (>95 %) in the optimized condition (35mg/3ml of chitosan in %1 AcOH, pH. 3, >98%, ITLC) was injected to wild-type rats followed by the biodistribution studies of the compound among the tissues excluding the injected knee data. Intra-articular injection of [166Ho]holmium chitosan complex to male wild-type rats and investigation of leakage of activity in the body showed that most of injected dose has remained in injection site 144 h after injection. Successful development and formulation of 166Ho-chitosan kit is described. This kit has the potential for use in clinical setting namely for radiosynovectomy and cancer radiochemotherapy.

It has been shown that some primary human tumors and their metastases, including prostate and breast tumors, over-express gastrin-releasing peptide (GRP) receptors. Bombesin is a neuropeptide with a high affinity for these GRP receptors. The purpose of this study was to prepare and evaluate the characteristics of a new Freeze-dried kit, [6-hydrazinopyridine-3-carboxylic acid (HYNIC)]-GABA-Bombesin [7-14] NH2 designed for the labeling with 99mTc using tricine and EDDA as coligand. Synthesis was performed on a solid phase using a standard Fmoc strategy and HYNIC precursor coupled at the N-terminus. Purified peptide conjugate was labeled with 99mTc at 100°C for 10 min. Radiochemical analysis involved ITLC and high-performance liquid chromatography methods. Peptide conjugate stability and affinity to human serum was challenged for 24 hours. The internalization rate was studied in GRP receptor expressing PC-3 cells. Biodistribution of radiopeptide was studied in rats. Radiolabeling was performed at high specific activities, and radiochemical purity was >98%. The stability of radiolabeled peptide in human serum was excellent. In vitro studies showed >14% of activity was specific internalized into PC-3 cells up to 4 h. After injection into rat biodistribution data showed a rapid bloodclearance, with renal excretion and specific binding towards GRP receptor-positive tissues such as pancreas (1.15±0.19% ID/g after 4 h). [99mTc-HYNIC]-GABA-Bombesin [7-14] NH2 showed favorable radiochemical and biological characteristics which make our new designed labeled peptide conjugate as a very suitable agent for diagnosticpurposes in malignant tumors.

Ubiquicidin (UBI) 29-41 is a synthetic antimicrobial peptide that binds with the microbial cell membrane at the location of infection. This study was conducted to evaluate its probable efficacy as an infection-imaging agent with potential to differentiate bacterial infection from sterile inflammation in humans. Fifteen diabetic foot patients (10 males and 5 females) with suspected bacterial infection, prior to starting antibiotic treatment, were selected for this study. First a routine three phase bone scan and later a 99mTc-UBI scan was performed for all the patients. 555-740 MBq of 99mTc-UBI was injected intravenously. A 10 minute dynamic study was followed by spot views of the suspected region of infection and corresponding normal areas (liver and kidneys) at 60 and 120 min. Whole-body anterior and posterior images were also acquired. To interpret the studies as positive or negative, visual score (0 -3) was used, with scores of 0 (minimal or no uptake; equivalent to soft tissue) and 1 (mild; less uptake than in liver) being considered negative and scores of 2 (moderate; uptake equal to or greater than that in liver) and 3 (intense uptake equal to or greater than that in kidneys) being considered positive. Of 15 studies performed with 99mTc-UBI, all had positive bacterial cultures. The result of bone scan was positive for osteomyelitis in 12 patients (80%). 99mTc-UBI Scintigraphy was positive in 6 patients, but negative in nine. The sensitivity of 99mTc-UBI for detection of infection was therefore 40%. From 12 patients who had positive bone scans, only 6 had a positive 99mTc-UBI (50%) indicating the sensitivity of 50% for 99mTc-UBI in osteomyelitis cases. 99mTc-UBI was not positive in any patient who had evidence of soft tissue infection in the bone scan. Although 99mTc-UBI 29-41 was well tolerated by all the patients without any side effects, considering low sensitivity of this agent, this radiopharmaceutical is not of great value for diabetic foot infection diagnosis.

[64Cu]diacetyl-bis(N4-methylthiosemicarbazone) ([64Cu]ATSM) is a well-established hypoxia imaging tracer with reproducible production and significant specifity. In this work the high yield production and quality control as well as imaging studies in healthy rabbits is reported. Copper-64 produced via the 68Zn(p,an)64Cu nuclear reaction (30 MeV protons at 180 µA) was used for the preparation of [64Cu]diacetyl-bis(N4-methylthiosemicarbazone)([64Cu]ATSM). Followed by quality control and administration to healthy rats as well as healthy rabbits for biodistribution and imaging studies respectively. 64Cu2+ (500 mCi, separation yield> 95%, radionuclide purity>96%) was used for [64Cu]ATSM production (radiochemical purity>99%, specific activity of 300 Ci/mmol) followed by administration to healthy rabbits and coincidence imaging demonstrating uptake in liver, kidney and bowel as shown by other reports in various rodents and human. [64Cu]ATSM radiopharmaceutical is produced and now available in large quantities for research and/or clinical trials in the country.

Journal clubs play an important role in teaching Evidence Based Medicine (EBM). Evidence based journal clubs focus on real problems of the group, and set a minimum level of evidence for articles to be presented, and in the end a clinical bottom line is set to be used in the daily clinical practice. In this article, we have explained our experience in running evidence based journal clubs in the previous year and the challenges in the path of this goal are discussed. Before starting the evidence based journal clubs, we set up several lectures on EBM for the teachers of the research center as well as the residents. From September 2010 to November 2010, we ran the journal clubs of our research center by a two-session plan: first identifying an important clinical question, second presenting the best available evidence. The assigned levels of evidence for evidence based journal clubs as well as previous traditional one were compared. Twelve journal clubs were presented in the study period: Five systematic reviews, 2 guidelines, 3 narrative review articles, and 2 individual articles. Ten out of 12 traditional journal club articles were narrative review articles and 2 were clinical guidelines. 41.6% of the evidence based journal clubs were assigned level 1 of evidence. In contrast 83.3% of traditional journal clubs were in the 4th level of evidence. Evidence based journal clubs can be very useful in improving the quality of presented articles in the journal clubs and are invaluable for teaching EBM

Radiolabeled antibiotics are being used for the specific diagnosis of infection by exploiting their specific binding properties to the bacterial components, thereby making it possible to differentiate infection from sterile lesions. The aim of this work was to prepare and evaluate a freeze-dried kit of ciprofloxacin designed for the labeling with 99mTc. Factors like amount of reducing agent and optimum pH were investigated to make the ciprofloxacin kit. The kit was reconstituted with 99mTc at room temperature and the radiochemical purity was evaluated by ITLC method. Stability and protein binding in human serum followed by in vitro binding to bacteria were assessed. Biodistribution of labeled kit in staphylococcus aureus infected rats muscles were studied using ex vivo counting and scintigraphy. Labeling yield of >90% was obtained corresponding to a specific activity of 178 GBq/mmol. The stability of radiolabeled kit in human serum was 84.2% after 1 hour post incubation. In-vitro studies showed 75 % of radioactivity was bound to bacteria. After injection into mice clearance from the circulation occurred mainly by biliary-renal clearance and site of infection was rapidly detected within 30 min. Target to non-target muscle ratio was 3.23 ± 0.05 % at 30 min post injection. 99mTc-ciprofloxacin showed favorable radiochemical and biological characteristics which permitted detection of the infection with optimal visualization.

This report presents a 3.5-year-old boy who was hospitalized for limping. Medical history and physical exams were not suggestive for any definitive diagnosis. Laboratory and radiographic exams did not support any specific diagnosis either. Subsequently bone scan was performed and increased activity in the ankle due to cuboid fracture was incidentally observed.

A 57-year-old male with history of prostatectomy, cyctectomy, cecal urinary diversion for invasive prostate cancer and with a recent rise in PSA level, was referred for bone scintigraphy to rule out osseous metastatic disease. An interesting finding was abnormal tracer accumulation throughout the large bowel, which was proved to be due to urinary diversion.