Asia Oceania Journal of Nuclear Medicine & Biology
Volume:3 Issue: 2, Spring 2015

Prostate cancer remains a major public health problem worldwide. Imaging plays an important role in the assessment of disease at all its clinical phases, including staging, restaging after definitive therapy, evaluation of therapy response, and prognostication. Positron emission tomography with a number of biologically targeted radiotracers has been demonstrated to have potential diagnostic and prognostic utility in the various clinical phases of this prevalent disease. Given the remarkable biological heterogeneity of prostate cancer, one major unmet clinical need that remains is the non-invasive imaging-based characterization of prostate tumors. Accurate tumor characterization allows for image-targeted biopsy and focal therapy as well as facilitates objective assessment of therapy effect. PET in conjunction with radiotracers that track the thymidine salvage pathway of DNA synthesis may be helpful to fulfill this necessity. We review briefly the preclinical and pilot clinical experience with the two major cellular proliferation radiotracers, [18F]-3’-deoxy-3’-fluorothymidine and [18F]-2’-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil in prostate cancer.

Improved brain uptake ratio (IBUR), employing 99mTc-ethyl cysteinate dimer (99mTc-ECD), is an automatic non-invasive method for quantitatively measuring regional cerebral blood flow (rCBF). This method was developed by the reconstruction of the theory and linear regression equation, based on rCBF measurement by H215O positron emission tomography. Clarification of differences in rCBF values obtained by Patlak plot (PP) and IBUR method is important for clinical diagnosis during the transition period between these methods. Our purpose in this study was to demonstrate the relationship between rCBF values obtained by IBUR and PP methods and to evaluate the clinical applicability of IBUR method. The mean CBF (mCBF) and rCBF values in 15 patients were obtained using the IBUR method and compared with PP method values. Overall, mCBF and rCBF values, obtained using these independent techniques, were found to be correlated (r=0.68). The mCBF values obtained by the IBUR method ranged from 18.9 to 44.9 ml/100g/min, whereas those obtained by the PP method ranged from 34.7 to 48.1 ml/100g/min. The rCBF values obtained by the IBUR method ranged from 16.3 to 60.2 ml/100g/min, whereas those obtained by the PP method were within the range of 26.7-58.8 ml/100g/min. The ranges of mCBF and rCBF values, obtained by the IBUR method, were approximately 60% lower than those obtained by the PP method; therefore, this method can be useful for diagnosing lower flow area. Re-analysis of prior PP data, using the IBUR method, could be potentially useful for the clinical follow-up of rCBF.

This study was designed to assess defect detectability in positron emission tomography (PET) imaging of abdominal lesions. A National Electrical Manufactures Association International Electrotechnical Commission phantom was used. The simulated abdominal lesion was scanned for 10 min using dynamic list-mode acquisition method. Images, acquired with scan duration of 1-10 min, were reconstructed using VUE point HD and a 4.7 mm full-width at half-maximum (FWHM) Gaussian filter. Iteration-subset combinations of 2-16 and 2-32 were used. Visual and physical analyses were performed using the acquired images. To sequentially evaluate defect detectability in clinical settings, we examined two middle-aged male subjects. One had a liver cyst (approximately 10 mm in diameter) and the other suffered from pancreatic cancer with an inner defect region (approximately 9 mm in diameter). In the phantom study, at least 6 and 3 min acquisition durations were required to visualize 10 and 13 mm defect spheres, respectively. On the other hand, spheres with diameters ≥17 mm could be detected even if the acquisition duration was only 1 min. The visual scores were significantly correlated with background (BG) variability. In clinical settings, the liver cyst could be slightly visualized with an acquisition duration of 6 min, although image quality was suboptimal. For pancreatic cancer, the acquisition duration of 3 min was insufficient to clearly describe the defect region. The improvement of BG variability is the most important factor for enhancing lesion detection. Our clinical scan duration (3 min/bed) may not be suitable for the detection of small lesions or accurate tumor delineation since an acquisition duration of at least 6 min is required to visualize 10 mm lesions, regardless of reconstruction parameters. Improvements in defect detectability are important for radiation treatment planning and accurate PET-based diagnosis.

Post-treatment evaluations by CT/MRI (based on the International Working Group/ Cotswolds meeting guidelines) and PET (based on Revised Response Criteria), were examined in terms of progression-free survival (PFS) in patients with malignant lymphoma (ML). 79 patients, undergoing CT/MRI for the examination of suspected lesions and whole-body PET/CT before and after therapy, were included in the study during April 2007-January 2013. The relationship between post-treatment evaluations (CT/MRI and PET) and PFS during the follow-up period was examined, using Kaplan-Meier survival analysis. The patients were grouped according to the histological type into Hodgkin’s lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), and other histological types. The association between post-treatment evaluations (PET or PET combined with CT/ MRI) and PFS was examined separately. Moreover, the relationship between disease recurrence and serum soluble interleukin-2 receptor, lactic dehydrogenase, and C-reactive protein levels was evaluated before and after the treatment. Patients with incomplete remission on both CT/MRI and PET had a significantly shorter PFS, compared to patients with complete remission on both CT/MRI and PET and those exhibiting incomplete remission on CT/MRI and complete remission on PET (P<0.001). Post-treatment PET evaluations were strongly correlated with patient outcomes in cases with HL or DLBCL (P<0.01) and other histological types (P<0.001). In patients with HL or DLBCL, incomplete remission on both CT/MRI and PET was associated with a significantly shorter PFS, compared to patients with complete remission on both CT/MRI and PET (P<0.05) and those showing incomplete remission on CT/MRI and complete remission on PET (P<0.01). In patients with other histological types, incomplete remission on both CT/MRI and PET was associated with a significantly shorter PFS, compared to cases with complete remission on both CT/MRI and PET (P<0.001). None of the serum parameters differed significantly between recurrent and non-recurrent cases. Post-treatment PET evaluations were well correlated with the outcomes of patients with ML, exhibiting FDG uptake. Among patients with HL or DLBCL, a post-treatment complete remission on PET was predictive of a relatively long PFS. For predicting the prognosis of patients with other histological types, a combination of CT/MRI and PET, rather than PET alone, is recommended.

In nuclear medicine studies, gallium-68 (68Ga) citrate has been recently known as a suitable infection agent in positron emission tomography (PET). In this study, by applying an in-house produced 68Ge/68Ga generator, a simple technique for the synthesis and quality control of 68Ga-citrate was introduced; followed by preliminary animal studies. 68GaCl3 eluted from the generator was studied in terms of quality control factors including radiochemical purity (assessed by HPLC and RTLC), chemical purity (assessed by ICP-EOS), radionuclide purity (evaluated by HPGe), and breakthrough. 68Ga-citrate was prepared from eluted 68GaCl3 and sodium citrate under various reaction conditions. Stability of the complex was evaluated in human serum for 2 h at 370C, followed by biodistribution studies in rats for 120 min. 68Ga-citrate was prepared with acceptable radiochemical purity (>97 ITLC and >98% HPLC), specific activity (4-6 GBq/mM), chemical purity (Sn, Fe) This study demonstrated the possible in-house preparation and quality control of 68Ga-citrate, using a commercially available 68Ge/68Ga generator for PET imaging throughout the country.

Peptide Receptor Radionuclide Therapy (PRRT) with yttrium-90 (90Y) and lutetium-177 (177Lu)-labelled SST analogues are now therapy option for patients who have failed to respond to conventional medical therapy. In-house production with automated PRRT synthesis systems have clear advantages over manual methods resulting in increasing use in hospital-based radiopharmacies. We report on our one year experience with an automated radiopharmaceutical synthesis system. All syntheses were carried out using the Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® automated synthesis system. All materials and methods used were followed as instructed by the manufacturer of the system (Eckert & Ziegler Eurotope, Berlin, Germany). Sterile, GMP-certified, no-carrier added (NCA) 177Lu was used with GMPcertifiedpeptide. An audit trail was also produced and saved by the system. The quality of the final product was assessed after each synthesis by ITLCSG and HPLC methods. A total of 17 [177Lu]-DOTATATE syntheses were performed between August 2013 and December 2014. The amount of radioactive [177Lu]-DOTATATE produced by each synthesis varied between 10-40 GBq and was dependant on the number of patients being treated on a given day. Thirteen individuals received a total of 37 individual treatment administrations in this period. There were no issues and failures with the system or the synthesis cassettes. The average radiochemical purity as determined by ITLC was above 99% (99.8 ± 0.05%) and the average radiochemical purity as determined by HPLC technique was above 97% (97.3 ± 1.5%) for this period. The automated synthesis of [177Lu]-DOTATATE using Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® system is a robust, convenient and high yield approach to the radiolabelling of DOTATATE peptide benefiting from the use of NCA 177Lu and almost negligible radiation exposure of the operators.

Herein, we report the F-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) findings of a benign solitary fibrous tumor (SFT) of the kidney. The patient was a 63-year-old woman with a mass in the right kidney (10×9.7 cm), incidentally found on CT images. The CT scan showed a lobulated tumor arising from the hilum of the right kidney. The tumor consisted of two components with different patterns of enhancement. Most of the tumor demonstrated moderate enhancement from the corticomedullary to nephrographic phase. A small nodular component at the caudal portion of the tumor showed avid enhancement in the corticomedullary phase and rapid washout in the nephrographic phase in contrast-enhanced CT. FDG-PET/CT was performed and showed weak FDG accumulation (SUVmax=2.30 and 1.91 in the main and small caudal components). Although renal cell carcinoma was preoperatively diagnosed, histopathological examination revealed renal SFT, with no malignant potential. Therefore, when a renal tumor with contrast-medium enhancement and low FDG accumulation is demonstrated, SFT should be considered as a differential diagnosis in addition to renal cell carcinoma.

Temporal bone chondroblastoma is an extremely rare benign bone tumor. We encountered two cases showing similar imaging findings on computed tomography (CT), magnetic resonance imaging (MRI), and dual-time-point 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT. In both cases, CT images revealed temporal bone defects and sclerotic changes around the tumor. Most parts of the tumor showed low signal intensity on T2- weighted MRI images and non-uniform enhancement on gadolinium contrast-enhanced T1-weighted images. No increase in signal intensity was noted in diffusion-weighted images. Dual-time-point PET/CT showed markedly elevated 18F-FDG uptake, which increased from the early to delayed phase. Nevertheless, immunohistochemical analysis of the resected tumor tissue revealed weak expression of glucose transporter-1 and hexokinase II in both tumors. Temporal bone tumors, showing markedly elevated 18F-FDG uptake, which increases from the early to delayed phase on PET/CT images, may be diagnosed as malignant bone tumors. Therefore, the differential diagnosis should include chondroblastoma in combination with its characteristic findings on CT and MRI.

The C7-RAS 6/061-004 training course by the International Atomic Energy Agency/Regional Cooperative Agreement (IAEA/RCA) was held in Chiba in 2014. The syllabus, pre- and post-course evaluations, and survey questionnaire results were assembled in this course. The post-course evaluation, including 32 questions similar to the pre-course evaluation, was performed right after the end of the final educational lecture. The mean score showed an improvement, with the score rising from 57.0 points at the beginning to 66.5 points at the end. Among 22 trainees, the greatest score was in a higher range, with an improvement from 82 points at the beginning to 88 points at the end. The grading distribution, with regard to the training course, was as follows: excellent (68.2%), good (31.8%), average (0%), fair (0%), and poor (0%). This report on the training course, held in Chiba in 2014, will contribute to the future global plans of IAEA/RCA. Continuous training courses in member states are required to decrease the present disparities in the knowledge level, instrumentation, and human resources.