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Objective(s): 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. Methods: The automated synthesis system we use is divided into three parts of a) servomotor modules, b) single use sterile synthesis cassettes and, c) a computerised 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. Results: 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 8.6x10-6% 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

18F-FDG positron emission tomography (PET) value for the assessment of neuro-endocrine tumours (NET) is limited. Preliminary studies indicate that 18F-DOPA and 68Ga-DOTA-NOC are more accurate for disease assessment and 68Ga-DOTA peptides provide additional data on receptor status that are crucial for targeted radionuclide therapy. At present, there are no comparative studies investigating their role in NET. The aim of this study was to compare 68Ga-DOTA-NOC and 18F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours. Thirteen patients with biopsy-proven NET (gastro-entero-pancreatic or pulmonary) were prospectively enrolled and scheduled for 18F-DOPA and 68Ga-DOTA-NOC PET. PET results obtained with both tracers were compared with each other, with other conventional diagnostic procedures (CT, ultrasound) and with follow-up (clinical, imaging). The most common primary tumour site was the pancreas (8/13) followed by the ileum (2/13), the lung (2/13) and the duodenum (1/13). The carcinoma was well differentiated in 10/13 and poorly differentiated in 3/13 cases. 68Ga-DOTA-NOC PET was positive, showing at least one lesion, in 13/13 cases while 18F-DOPA PET was positive in 9/13. On a lesions basis, 68Ga-DOTA-NOC identified more lesions than 18F-DOPA (71 vs 45), especially at liver, lung and lymph node level. 68Ga-DOTA-NOC correctly identified the primary site in six of eight non-operated cases (in five cases, the primary was surgically removed before PET), while 18F-DOPA identified the primary only in two of eight cases. Although the patients studied are few and heterogeneous, our data show that 68Ga-DOTA-NOC is accurate for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours in either the primary or metastatic site and that it offers several advantages over 18F-DOPA. [ABSTRACT FROM AUTHOR]

Background/Aim: The mode of action of the somatostatin analog octreotide on neuro-endocrine tumour proliferation is largely unknown. Overexpression of the proto-oncogene Akt/PKB (protein kinase B) has been demonstrated in certain neuro-endocrine tumours: Akt activates downstream proteins including mTOR and p70S6K, which play an important role in cell proliferation. RAD001 (everolimus) is a novel agent that is being trialled in the treatment of neuro-endocrine tumours, and is known to interact with mTOR. We explored the mechanism of action of octreotide, RAD001, and their combination on cell proliferation and kinase activation in a neuro-endocrine tumour cell line (rat insulinoma cell line, INS1). Methods: Proliferation assays were used to determine the effects of octreotide, RAD001, and their combination on cell proliferation. Western blotting was used to characterize the expression of phosphorylated Akt, phosphorylated TSC2, phosphorylated mTOR, and phosphorylated 70S6K. Results: Treatment with octreotide and RAD001 inhibited proliferation and attenuated phosphorylation of all downstream targets of Akt: TSC2, mTOR, and p70S6K. Conclusions: In this cell model, octreotide and RAD001 appear to act through a similar pathway and inhibit the Akt-mTOR-p70S6 kinase pathway downstream of Akt. There may be some overlapping effects of the two inhibitors on the mTOR pathway, although it is likely that other additional effects may differentiate the two agents. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Radionuclide therapy has distinct similarities to, but also profound differences from external radiotherapy. This review discusses techniques and results of previously developed dosimetry methods in thyroid carcinoma, neuro-endocrine tumours, solid tumours and lymphoma. In each case, emphasis is placed on the level of evidence and practical applicability. Although dosimetry has been of enormous value in the preclinical phase of radiopharmaceutical development, its clinical use to optimise administered activity on an individual patient basis has been less evident. In phase I and II trials, dosimetry may be considered an inherent part of therapy to establish the maximum tolerated dose and dose–response relationship. To prove that dosimetry-based radionuclide therapy is of additional benefit over fixed dosing or dosing per kilogram body weight, prospective randomised phase III trials with appropriate end points have to be undertaken. Data in the literature which underscore the potential of dosimetry to avoid under- and overdosing and to standardise radionuclide therapy methods internationally are very scarce. In each section, particular developments and insights into these therapies are related to opportunities for dosimetry. The recent developments in PET and PET/CT imaging, including micro-devices for animal research, and molecular medicine provide major challenges for innovative therapy and dosimetry techniques. Furthermore, the increasing scientific interest in the radiobiological features specific to radionuclide therapy will advance our ability to administer this treatment modality optimally. [ABSTRACT FROM AUTHOR]

A 59 year old patient was referred to our department to detect disease activity related to clinical symptoms of tiredness, weight loss and an elevated serum serotonine, suspicious of a neuro-endocrine tumour. A 18F-fluoro-l-dihydroxy-phenylalanine (FDOPA) PET/CT scan was performed, which showed focally increased uptake in the terminal ileum and in a mesenterial lymph node. Additionally, an area of intense uptake was observed intracranially. Histological analysis confirmed the presence of a WHO grade I meningioma. Few cases of FDOPA PET uptake in meningiomas have been published, underlining it is as a rare finding. Awareness of this potential finding is crucial to avoid misinterpretation as intracerebral metastasis. [ABSTRACT FROM AUTHOR]