Current Radiopharmaceuticals - Volume 9, Issue 2, 2016

Background and Objective: Radioactive seed localization (RSL) is a new technique for surgical identification of nonpalpable breast lesions. We describe the preparation of the needle with I-125 seeds for ultrasound-guided deposition in breast lesions. In a feasibility study we investigated the minimum activity amount needed for reliable gamma probe identification of the seeds and the levels of exposure to the staff. Methods: 11 patients received a seed, which was manually placed in an 18 gauge needle with bone wax occluding the tip, and the radiologist introduced it into the breast tissue guided by ultrasound. The seed was located during the operation with a handheld gamma probe. The activity amount required was studied in a water bath. Radiation exposure to the fingertips of pathologists was measured by a thermoluminescent dosemeter. Results: All seeds were successfully prepared, positioned in the breast lesion, and easily identified. The surgeon removed the seeds together with the breast lesions, and they were identified by the pathologist. There were no unexpected adverse drug reactions. Water bath studies suggest that 1-3 MBq I-125 was sufficient for precise identification, regardless of the presence of conventional Tc- 99m activity from sentinel node injection. The total finger dose exposure to the pathologists for the 8 procedures was below the detection limit of 0.1 mSv. Conclusion: I-125 seeds for ultrasound-guided deployment and surgical identification of breast lesions were successfully prepared and identified for this promising new radioguided surgical technique. The radiation exposure to staff involved is considerably below the permissible limits and almost negligible.

Background and Objective: 18F-Fluorocholine has been suggested as one of the reputable imaging tracers for diagnosis of prostate tumour in Positron Emission Tomography / Computed Tomography (PET/CT) modality. Nevertheless, it has never been synthesised in Malaysia. We acknowledged that the major problem with 18F-Fluorocholine is due to its relatively low radiochemical yield at the end of synthesis (EOS). Therefore, this article presents improved 18FFluorocholine radiochemical yields after carrying out optimisation on azeotropic drying of 18F-Fluorine. Methods: In the previous study, the azeotropic drying of non-carrier-added (n.c.a) 18F-Fluorine in the reactor was conducted at atmospheric pressure (0 atm) and shorter duration time. In this study, however, the azeotropic drying of non-carried-added (n.c.a) 18FFluorine was made at a high vacuum pressure (- 0.65 to - 0.85 bar) with an additional time of 30 seconds. At the end of the synthesis, the mean radiochemical yield was statistically compared between the two azeotropic drying conditions so as to observe whether the improvement made was significant to the radiochemical yield. Results: From the paired sample t-test analysis, the improvement done to the azeotropic drying of non-carrier-added (n.c.a) 18F-Fluorine was statistically significant (p < 0.05). With the improvement made, the 18F-Fluorcholine radiochemical yield was found to have increase by one fold. Conclusion: Improved 18F-Fluorocholine radiochemical yields were obtained after the improvement had been done to the azeotropic drying of non-carrier-added (n.c.a) 18F-Fluorine. It was also observed that improvement made to the azeotropic drying of non-carrier-added (n.c.a) 18F-Fluorine did not affect the 18F-Fluorocholine quality control analysis.

Background and Objective: Prostate cancer continues to be the most prevalent cancer in men in Malaysia. As time progresses, the prospect of PET imaging modality in diagnosis of prostate cancer is promising, with on-going improvement on novel tracers. Among all tracers, 18F-Fluorocholine is reported to be a reputable tracer and reliable diagnostic technique for prostate imaging. Nonetheless, only 18F-Fluorodeoxyglucose (18F-FDG) is available and used in most oncology cases in Malaysia. With a small scale GMP-based radiopharmaceuticals laboratory set-up, initial efforts have been taken to put Malaysia on18F-Fluorocholine map. This article presents a convenient, efficient and reliable method for quality control analysis of 18F-Fluorocholine. Besides, the aim of this research work is to assist local GMP radiopharmaceuticals laboratories and local authority in Malaysia for quality control analysis of 18F-Fluorocholine guideline. Methods: In this study, prior to synthesis, quality control analysis method for 18F-Fluorocholine was developed and validated, by adapting the equipment set-up used in 18F-Fluorodeoxyglucose (18FFDG) routine production. Quality control on the 18F-Fluorocholine was performed by means of pH, radionuclidic identity, radio-high performance liquid chromatography equipped with ultraviolet, radio- thin layer chromatography, gas chromatography and filter integrity test. Results: Post-synthesis; the pH of 18F-Fluorocholine was 6.42 ± 0.04, with half-life of 109.5 minutes (n = 12). The radiochemical purity was consistently higher than 99%, both in radio-high performance liquid chromatography equipped with ultraviolet (r-HPLC; SCX column, 0.25 M NaH2PO4: acetonitrile) and radio-thin layer chromatography method (r-TLC). The calculated relative retention time (RRT) in r-HPLC was 1.02, whereas the retention factor (Rf) in r-TLC was 0.64. Potential impurities from 18F-Fluorocholine synthesis such as ethanol, acetonitrile, dimethylethanolamine and dibromomethane were determined in gas chromatography. Using our parameters, (capillary column: DB-200, 30 m x 0.53 mm x 1 um) and oven temperature of 35°C (isothermal), all compounds were well resolved and eluted within 3 minutes. Level of ethanol and acetonitrile in 18F-Fluorocholine were detected below threshold limit; less than 5 mg/ml and 0.41 mg/ml respectively. Meanwhile, dimethylethanolamine and dibromomethane were undetectable. Conclusion: A convenient, efficient and reliable quality control analysis work-up procedure for 18FFluorocholine has been established and validated to comply all the release criteria. The convenient method of quality control analysis may provide a guideline to local GMP radiopharmaceutical laboratories to start producing 18F-Fluorocholine as a tracer for prostate cancer imaging.

Background and Objective: The design of target-specific molecular imaging probes to determine infection sites are mainly based on the biochemistry of the inflammatory response that may lead to an ideal agent for infection imaging. Infectious diseases timely and specifically diagnosed can be clinically challenging but essential for the patient’s recovery. Laboratory tests can detect the responsible microorganism but cannot discriminate between sterile inflammatory disease and truly infectious disease. On the other hand, scintigraphic images, can pinpoint the infection in the body. Methods: Bacteriophages (phages) are viruses that infect specific bacterial strains. Given the composition of the protein capsid, they could be used as radiopharmaceuticals to diagnose bacterial infection. In this case, PP7 phage was labelled and evaluated as a specific tracer for Pseudomonas aeruginosa infections. 99mTc-Phage synthesis used HYNIC as a bifunctional agent. Physicochemical evaluation included studies such as stability in time, ligand exchange, lipophilicity and bacterial binding assay. Three groups of animals namely; healthy, infected with Pseudomonas aeruginosa and induced sterile inflammation were used to conduct biological evaluation Results: The radiolabelling process required size exclusion purification of the 99mTc-Phage, which was obtained with a radiochemical purity higher than 90%, during 18 hours post labelling. The collective accumulation in the stomach, small intestine and large intestine and thyroid of 99mTc-Phage was negligible, indicating no in vivo reoxidation. The complex presented urinary elimination. Target/ non-target ratio (T/NT) was determined both for sterile inflammation and for infection. Values were 2.5 ± 0.4 and 4.2 ± 0.3 respectively. These values indicate significant differences between sterile inflammation and infection by Pseudomonas aeruginosa (p<0.05 unpaired two sided t-test). Conclusion: Targeted biodistribution profile and good T/NT ratios, indicate that this complex presents enough specificity to discriminate between infection caused by Pseudomonas aeruginosa and sterile inflammation.

Radioactive seed localization (RSL) is a new technique for surgical identification of non-palpable breast lesions. We describe the preparation of the needle with I-125 seeds for ultrasound-guided deposition in breast lesions. In a feasibility study we investigated the minimum activity amount needed for reliable gamma probe identification of the seeds and the levels of exposure to the staff. Methods: 11 patients received a seed, which was manually placed in an 18 gauge needle with bone wax occluding the tip, and the radiologist introduced it into the breast tissue guided by ultra-sound. The seed was located during the operation with a handheld gamma probe. The activity amount required was studied in a water bath. Radiation exposure to the fingertips of pathologists was measured by a thermoluminescent dosemeter. Results: All seeds were successfully prepared, positioned in the breast lesion, and easily identified. The surgeon removed the seeds together with the breast lesions, and they were identified by the pathologist. There were no unexpected adverse drug reactions. Water bath studies suggest that 1-3 MBq I-125 was sufficient for precise identification, regardless of the presence of conventional Tc- 99m activity from sentinel node injection. The total finger dose exposure to the pathologists for the 8 procedures was below the detection limit of 0.1 mSv. Conclusion: I-125 seeds for ultrasound-guided deployment and surgical identification of breast lesions were successfully prepared and identified for this promising new radioguided surgical technique. The radiation exposure to staff involved is considerably below the permissible limits and almost negligible.

Purpose: To assess changes in social and neuro-cognition and regional cerebral blood flow (rCBF) in schizophrenic patients with psychotic syndrome treated with Social Skill Training (SST). Methods: 17 patients underwent two high resolution rCBF SPECT at rest before and after a one-year treatment with SST. Patients were assessed using a neuropsychological evaluation (W.A.I.S.-R, T.M.T, Verbal Fluency, W.C.S.T.). SPM8 was used to investigate rCBF changes from the pre- to the post-SST condition and the relationship between rCBF and clinical scores used as covariates of interest. Results: All patients presented with an improvement in social perception, ability to deal with abstract social conventions, rules and judgments about people (Comprehension and Picture Completion sub-tests) and some neuro-cognitive functions sustaining the process of socially relevant information. The main effect of SST was to produce rCBF increases in precuneus, PCC, superior parietal lobules, PMC, pre-SMA, precentral gyrus, dmPFC, dlPFC, vmPFC, OFC (p<0.0001 uncorrected). The SPM analysis showed that Comprehension was supported by PMC, dmPFC, OFC and vmPFC, while the Picture Completion was supported by PMC and dmPFC (p<0.0001). Conclusion: SST in schizophrenic patients improves resting neural activity in cortical areas of the amigdala-based and non-amygdala networks of social brain, including dmPFC and vmPFC, and dlPFC, which are known to be part of default mode and task-positive networks and to be implicated in schizophrenia.

Background and Objectives: The aim of the study is to evaluate the therapeutic efficacy and safety of Yttrium- 90 radiolabelled chimeric anti CD20 antibody-Rituximab in the treatment of patients with relapsed/ refractory B cell Non-Hodgkins Lymphoma (NHL). Methods: Twenty patients with relapsed/refractory CD20+ NHL in progressive state were included in the study. These patients had undergone a median of 2 (range 2-5) prior standard chemotherapy ± immunotherapy regimens. All the patients received rituximab 250 mg/m2 on days 1 and 8, and either 14 MBq/kg (0.4 mCi/kg) or 11 MBq/kg (0.3 mCi/kg) of Y-90 Rituximab on day 8 (maximum dose, 32 mCi) depending upon their platelet count. The patients were observed for systemic toxicity and response for at least 12 weeks after therapy. Results: No acute adverse effects were observed after the administration of 90Y-Rituximab. Overall response rate (ORR) was 45% of which complete response (CR) was observed in 2 patients, stable disease in 1 patient and partial response in 6 patients. The therapy was well tolerated with grade IV thrombocytopenia, neutropenia and anemia observed in 3, 4 and 2 patients respectively. Conclusion: 90Y-Rituximab therapy is safe and well tolerated in high risk extensively pretreated NHL patients. Toxicity is primarily hematologic, transient and reversible.

Purpose: We aim to assess the diagnostic and prognostic values of 18Ffluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in a small population with male breast cancer (MBC). Materials and Methods: From May 2005 to Jul 2013, we retrospectively reinterpreted 31 FDG PET/CT scans of 25 men (mean age: 67 years; range: 51-81 years) with a proven breast cancer diagnosis, from two Italian centers. In the majority of patients, an invasive ductal cancer was present (68%). PET/CT scan was performed for initial staging in 5 (16%), restaging in 18 (58%), restaging for the increase of tumor markers in 4 (13%), response to therapy in 2 (6%) and during follow-up in 2 cases (6%). The prognostic impact of PET/CT in this male breast cancer population was assessed by using Kaplan-Meier analysis. Results: Nuclear medicine imaging was negative in 10 subjects while it resulted positive in the residual 15 patients (60%). At initial staging, in four out of five cases, PET/CT showed a significant uptake in the primary cancer and of those three had also a loco-regional lymphatic and distant metastatic involvement. In restaging setting, PET/CT was more accurate than conventional imaging for detection of distant metastases, resolving two false-positive findings. Finally, a positive PET/CT scan was demonstrated to be prognostically unfavorable as compared to a negative exam. Conclusions: MBC is a rare tumor with similar biological and metabolic characteristics of female breast cancer. FDG PET/CT seems to be useful, particularly in the restaging setting, to delineate the correct therapeutic approach and to predict the prognosis.