Asia Oceania Journal of Nuclear Medicine & Biology
Volume:2 Issue: 2, Spring 2014

Gallium‐68 (Ga‐68) is an ideal research and hospital‐based PET radioisotope. Currently, the main form of Ga‐68 radiopharmaceutical that is being synthesised in‐house is Ga‐68 conjugated with DOTA based derivatives. The development of automated synthesis systems has increased the reliability, reproducibility and safety of radiopharmaceutical productions. Here we report on our three year, 500 syntheses experience with an automated system for Ga‐68 DOTATATE. The automated synthesis system we use is divided into three parts of a) servomotor modules, b) single use sterile synthesis cassettes and, c) a computerized system that runs the modules. An audit trail is produced by the system as a requirement for GMP production. The required reagents and chemicals are made in‐. The Germanium breakthrough is determined on a weekly basis. Production yields for each synthesis are calculated to monitor the performance and efficiency of the synthesis. The quality of the final product is assessed after each synthesis by ITLC‐SG and HPLC methods. A total of 500 Ga‐68 DOTATATE syntheses (>800 patient doses) were performed between March 2011 and February 2014. The average generator yield was 81.3±0.2% for 2011, 76.7±0.4% for 2012 and 75.0±0.3% for 2013. Ga‐68 DOTATATE yields for 2011, 2012, and 2013 were 81.8±0.4%, 82.2±0.4% and 87.9±0.4%, respectively. These exceed the manufacturer’s expected value of approximately 70%. Germanium breakthrough averaged 8.6×10‐6% of total activity which is well below the recommended level of 0.001%. The average ITLC‐measured radiochemical purity was above 98.5% and the average HPLC‐measured radiochemical purity was above 99.5%. Although there were some system failures during synthesis, there were only eight occasions where the patient scans needed to be rescheduled. In our experience the automated synthesis system performs reliably with a relatively low incident of failures. Our system had a consistent and reliable Ga‐68 DOTATATE output with high labelling efficiency and purity. There is minimal operator intervention and radiation exposure. The system is GMP‐compliant and has low maintenance and acceptable running costs. This system together with the recommended 68Ge/68Ga generator is well suited for use in a hospital‐based radiopharmacy

We performed a phase IIa clinical trial of trans-1-amino-3-18Ffluoro-cyclobutane carboxylic acid (anti-18F-FACBC), a synthetic amino acid analog for PET, in patients with metastatic prostate cancer. The study subjects consisted of 10 untreated prostate cancer patients having lymph node and/or bone metastasis. Five patients underwent whole-body PET 5 and 30 min after intravenous injection of anti-18F-FACBC. The other five patients underwent 60 min dynamic PET of the pelvis. Safety assessment was performed before and 24 h after injection. PET/CT images were assessed visually, and time courses of anti-18F-FACBC uptake were evaluated from dynamic imaging. Two mild adverse events were observed and resolved without treatment. All 10 patients showed increased accumulation of anti-18F-FACBC in the primary prostate lesion. CT revealed five enlarged lymph nodes indicating metastasis, and all showed increased uptake. Additionally, anti-18F-FACBC PET delineated unenlarged lymph nodes as hot spots. Anti-18F-FACBC PET demonstrated metastatic bone lesions, similar to conventional imaging. In one of two patients with lung metastasis, some lesions showed increased uptake. Regarding the time course, increased uptake of anti-18F-FACBC in the lesion was demonstrated immediately after injection, followed by gradual washout. The results of this phase IIa clinical trial indicated the safety of anti-18F-FACBC in patients with prostate cancer and the potential of anti-18F-FACBC PET to delineate primary prostate lesions and metastatic lesions. This clinical trial was registered as JapicCTI-101326.

The aim of this research was the development of 111In-labeled porphyrins as possible radiopharmaceuticals for the imaging of tumors. Ligands, 5, 10, 15, 20-tetrakis (3, 5-dihydroxyphenyl) porphyrin) (TDHPP), 5, 10, 15, 20-tetrakis (4-hydroxyphenyl) porphyrin (THPP) and 5, 10, 15, 20-tetrakis (3,4-dimethoxyphenyl) porphyrin) (TDMPP) were labeled with 111InCl3 (produced from proton bombardment of natCd target) in 60 min at 80ºC. Quality control of labeled compounds was performed via RTLC and HPLC followed by stability studies in final formulation and presence of human serum at 37ºC for 48 h as well as partition coefficient determination. The biodistribution studies performed using tissue dissection and SPECT imaging up to 24h. The complexes were prepared with >99% radiochemical purity (HPLC and RTLC), high stability in 48h. Partition coefficients (calculated as log P) for 111In-TDHPP, 111In-THPP and 111In-TDMPP were 0.88, 0.8 and 1.63 respectively. Due to urinary excretion with fast clearance for 111In-TDMPP, this complex is probably a suitable candidate for considering as a possible tumor imaging agent.

In order to evaluate the effect of post-reconstruction Gaussian filtering on image quality and myocardial blood flow (MBF) measurement by dynamic N-13 ammonia positron emission tomography (PET), we compared various reconstruction and filtering methods with image characteristics. Dynamic PET images of three patients with coronary artery disease (male-female ratio of 2:1; age: 57, 53, and 76 years) were reconstructed, using filtered back projection (FBP) and ordered subset expectation maximization (OSEM) methods. OSEM reconstruction consisted of OSEM_2I, OSEM_4I, and OSEM_6I with 2, 4, and 6 iterations, respectively. The images, reconstructed and filtered by Gaussian filters of 5, 10, and 15 mm, were obtained, as well as non-filtered images. Visual analysis of image quality (IQ) was performed using a 3-grade scoring system by 2 independent readers, blinded to the reconstruction and filtering methods of stress images. Then, signal-to-noise ratio (SNR) was calculated by noise and contrast recovery (CR). Stress and rest MBF and coronary flow reserve (CFR) were obtained for each method. IQ scores, stress and rest MBF, and CFR were compared between the methods, using Chi-square and Kruskal-Wallis tests. In the visual analysis, IQ was significantly higher by 10 mm Gaussian filtering, compared to other sizes of filter (PP=0.923 and 0.855 for readers 1 and 2, respectively). SNR was significantly higher in 10 mm Gaussian filter. There was a significant difference in stress and rest MBF between several vascular territories. However CFR was not significantly different according to various filtering methods. Post-reconstruction Gaussian filtering with a filter size of 10 mm significantly enhances the IQ of N-13 ammonia PET-CT, without changing the results of CFR calculation.

IQSPECT is an advanced high-speed SPECT modality for performing myocardial perfusion imaging (MPI), which uses a multi-focus fan beam collimator with resolution recovery reconstruction. The aim of this study was to compare IQSPECT compared with conventional SPECT interms of performance based on standard clinical protocols. In addition, we examined the concordance between conventional and IQSPECT in patients with coronary artery disease (CAD). Fifty-three patients undergoing rest-gated MPI for the evaluation of known or suspected coronary artery disease were enrolled in this study. In each patient, conventional SPECT (99mTc-tetrofosmin, 9.6 min; 201Tl, 12.9 min) was performed, immediately followed by IQSPECT, using a short acquisition time (4.3 min for 99mTc-tetrofosmin and 6.2 min for 201Tl). A quantitative analysis was performed on an MPI polar map using a 20-segment model of the left ventricle. An automated analysis by gated SPECT was carried out to determine the left ventricular volume and function, including the end-diastolic volume, end-systolic volume and left ventricular ejection fraction (LVEF). The degree of concordance between conventional SPECT and IQ-SPECT images was evaluated according to linear regression and Bland-Altman analyses. The segmental percent uptake exhibited a significant correlation between IQSPECT and conventional SPECT (P<0.05). The mean differences in 99mTc‐tetrofosmin studies were 1.1±6.6% (apex), 2.8±5.7% (anterior wall), 2.9±6.2% (septal wall),4.9±6.7% (lateral wall), and 1.8±5.6% (inferior wall). Meanwhile, regarding the 201Tl‐SPECT studies, these values were 1.6±6.9%, 2.0±6.6%, 2.1±5.9%, 3.3±7.2%, and 2.4±5.8%, respectively. Although the mean LVEF in IQ‐SPECT tended to be higher than that observed in conventional SPECT (conventional SPECT=64.8±11.8% and IQSPECT=68.3±12.1% for 99mTc‐tetrofosmin; conventional SPECT= 56.0±11.7% and IQSPECT=61.5±12.2% for 201Tl), quantitative parameters were not significantly different between IQ‐SPECT and conventional SPECT. According to the 99mTc‐tetrofosmin and 201Tl protocols, IQ‐SPECT images were comparable to and in agreement with conventional SPECT images. Our results suggest that IQ‐SPECT is a useful technology for MPI SPECT, and can lead to an increase in scan efficiency and patient comfort.

Diagnostic nuclear medicine is being increasingly employed in clinical practice with the advent of new technologies and radiopharmaceuticals. The report of the prevalence of a certain disease is important for assessing the quality of that article. Therefore, this study was performed to evaluate the quality of published nuclear medicine articles and determine the frequency of reporting the prevalence of studied diseases. We used Standards for Reporting of Diagnostic Accuracy (STARD) and Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklists for evaluating the quality of articles published in five nuclear medicine journals with the highest impact factors in 2012. The articles were retrieved from Scopus database and were selected and assessed independently by two nuclear medicine physicians. Decision concerning equivocal data was made by consensus between the reviewers. The average STARD score was approximately 17 points, and the highest score was 17.19±2.38 obtained by the European Journal of Nuclear Medicine. QUADAS-2 tool showed that all journals had low bias regarding study population. The Journal of Nuclear Medicine had the highest score in terms of index test, reference standard, and time interval. Lack of clarity regarding the index test, reference standard, and time interval was frequently observed in all journals including Clinical Nuclear Medicine, in which 64% of the studies were unclear regarding the index test. Journal of Nuclear Cardiology had the highest number of articles with appropriate reference standard (83.3%), though it had the lowest frequency of reporting disease prevalence (zero reports). All five journals had the same STARD score, while index test, reference standard, and time interval were very unclear according to QUADAS-2 tool. Unfortunately, data were too limited to determine which journal had the lowest risk of bias. In fact, it is the author’s responsibility to provide details of research methodology so that the reader can assess the quality of research articles. Five nuclear medicine journals with the highest impact factor were comparable in terms of STARD score, although they all showed lack of clarity regarding index test, reference standard, and time interval, according to QUADAS-2. The current data were too limited to determine the journal with the lowest bias. Thus, a comprehensive overview of the research methodology of each article is of paramount importance to enable the reader to assess the quality of articles.

Although thallium-201 exercise scintigraphy has been established for the detection of myocardial ischemia and viability, little is known regarding the myocardial thallium-201 kinetics during angioplasty. Herein, we report a 77-year old man with angina pectoris, in whom serial myocardial imaging after a single dose of thallium-201 was helpful in identifying not only the culprit lesion and myocardial viability, but also the dynamic changes in myocardial perfusion during angioplasty. Thallium-201 images after exercise showed a perfusion defect in the inferior wall, with a trivial redistribution 3 hours after the exercise and a marked improvement 24 hours later. Coronary angiography, performed 27 hours after exercise scintigraphy, showed severe stenosis in the right coronary artery. Guidewire crossing of the lesion interrupted the antegrade flow, which was restored after balloon dilation and stent implantation. Thallium-201 images, 2 hours after angioplasty (i.e., 30 hours after exercise), showed a decreased tracer uptake in the inferior wall, which improved the next day (i.e., 48 hours after exercise). Cardiac biomarkers were negative in the clinical course.

Radionuclide therapy is widely used as an effective modality in the management of bone pain. The main indication for this treatment is symptomatic bone metastases, confirmed by bone scintigraphy. We present a case of small cell lung cancer (SCLC) stage T4N2M1b, with a good metabolic response to systemic therapy and radiotherapy of the primary tumor and locoregional disease, which became metabolically less active and remarkably smaller in size (reduction to 1/6 of the original volume). In spite of the good overall response, the patient developed a syndrome with severe bone pain and had progression in the bone marrow metastases, confirmed by 18F-FDG PET/CT. The patient received 153Sm-EDTMP treatment with a good clinical response. However, in the whole body bone scan with the therapeutic dose, there was no visual evidence of bone metastasis. Retrospectively, by drawing the region of interest, it was possible to identify one metastatic site. The possible mechanisms of the efficacy of this treatment modality, in this specific setting, are also discussed.

Herein, we report a case of sentinel lymph node mapping in a uterine cervix cancer patient, referring to the nuclear medicine department of our institute. Lymphoscintigraphy images showed inappropriate intra‐cervical injection of radiotracer. Blue dye technique was applied for sentinel lymph node mapping, using intra‐cervical injection of methylene blue. Two blue/cold sentinel lymph nodes, with no pathological involvement, were intra‐operatively identified, and the patient was spared pelvic lymph node dissection. The present case underscores the importance of lymphoscintigraphy imaging in sentinel lymph node mapping and demonstrates the added value of blue dye injection in selected patients. It is suggested that preoperative lymphoscintigraphy imaging be considered as an integral part of sentinel lymph node mapping in surgical oncology. Detailed results of lymphoscintigraphy images should be provided for surgeons prior to surgery, and in case the sentinel lymph nodes are not visualized, use of blue dye for sentinel node mapping should be encouraged.

An inflammatory pseudotumor (IPT) is a rare benign lesion, characterized by nonneoplastic proliferation of inflammatory cells and presence of intermingling collagen fibers. IPT commonly occurs in the lungs and orbita, while an intraspinal IPT is extremely rare. IPT can mimic both clinically and radiologically malignant processes, and making a definitive preoperative diagnosis is often difficult. Recently, 18-fluorine fluorodeoxyglucose (18F-FDG) has been reported to accumulate in IPT in the lung, spleen, liver, pancreas, colon, orbit, mediastinum, and mesentery. However, to the best of our knowledge, accumulation of 18F-FDG has not been reported in lumbosacral intraspinal IPT. Herein, we report a case of IPT in the epidural space of the lumbar spine, using the imaging findings of 18F-FDG positron emission tomography-computed tomography (PET/CT) and contrastenhanced magnetic resonance imaging (MRI). This is the first case of IPT in the epidural space, depicted by 18F-FDG PET/CT, which revealed a homogeneous, intense 18F-FDG uptake.

In 1955, the first nuclear medicine division was established in Thailand by Professor Romsai Suwannik in the Department of Radiology, Siriraj Hospil, Mahidol University in Bangkok. In 1959 four years later, the second nuclear medicine division was established in the Department of Radiology, Chulalongkorn Hospital in Bangkok. The third nuclear medicine division was started in Rajvithi Hospital in Bangkok in 1961. The fourth nuclear medicine division was installed in Chiang Mai University which is the first University located outside of Bangkok in 1965 by Professor Dusadee Prabhasavat and Professor Sanan Simarak, ten years after the first nuclear medicine division in Siriraj Hospital. At the present in Thailand, there are twenty-five organizations providing clinical nuclear medicine services. Five medical faculties provide three years nuclear medicine residency training. There are eight companies which supply radiopharmaceuticals and/or nuclear medicine instruments one of these belongs to governmental office of atomic for peace (OAP of Thailand). In Nuclear medicine researches and clinical practices in Thailand had been progressed from the past to the present time and will more progress in the near future, which certainly is the part of Asian countries and ARCCNM.