Production and quality control of [(90)Y]DOTATOC for treatment of metastatic neuroendocrine tumors: results of 85 syntheses.

The aim of this paper was to describe the optimized labeling protocol and quality control measures used in the production of [(90)Y]DOTATOC, starting from three different radioactivity levels to treat one, two, or three patients per therapeutic session. We investigated three different starting radioactivity levels. For the low radioactivity preparation we used 5138±280 MBq of [Y] isotope, for the medium radioactivity preparation we used 8893±900 MBq, and for the high radioactivity preparation we used 11250±715 MBq. The radiochemical purity levels for the low radioactivity preparation, medium radioactivity preparation, and high radioactivity preparation were 99.95±0.09, 99.84±0.34, and 99.84±0.53%, respectively, and the radiochemical yields of the labeling procedures were 77.52±1.28, 75.53±3.72, and 78.00±3.20%, respectively. Media fill validation of the process was performed, and the parameters of pH, bacterial endotoxins, sterility, and osmolality were tested at process control. All radiopharmaceutical preparations satisfied the predetermined specifications fixed in our protocol regardless of the starting radioactivity level. The validation of the method guaranteed the safety and quality of the final products, contributing to providing the basis for constructing an informative and successful clinical trial.

Description of high purity and high specific activity of [11C]Choline synthesis using TRACERlab FXc module, and detailed report of quality controls.

We proposed a method of synthesis to produce [11C]Choline using TRACERlab FXc module that utilized gas phase iodination. The product had radiochemical purity of 99.79 ± 0.14 % and specific activity of 45.7 ± 7.59 GBq/µmol. [11C]Choline did not have at the moment a specific monograph in European Pharmacopeia therefore we used, when possible, as quality controls reference the monograph of [18F]FDG and we proposed suitable methods to verify radiochemical purity and to quantify residual DMAE and choline amounts.

Final results of a phase 2A study for the treatment of metastatic neuroendocrine tumors with a fixed activity of 90Y-DOTA-D-Phe1-Tyr3 octreotide.

BACKGROUND: The objective of this study was to assess the efficacy of (90)Y-DOTA-D-Phe1-Tyr3 octreotide ((90)Y-DOTATOC) therapy with a fixed activity of 2.56 GigaBequerels bimonthly in patients with advanced stage, well differentiated neuroendocrine carcinomas. METHODS: In total, 38 patients were enrolled in this phase 2A protocol. All patients had gastroenteropancreatic neuroendocrine tumors in sharp clinical and radiologic progression despite previous surgery, chemotherapy, and biotherapy. Their survival rate after therapy with (90)Y-DOTATOC was compared with a chronologic control group of patients who had received biotherapy and chemotherapy and with results from a previous similar study. The progression-free survival rate after peptide receptor radionuclide therapy with (90)Y-DOTATOC was determined for all patients until they had documented disease progression according to Response Criteria in Solid Tumors, tumor-related death, or censoring. RESULTS: Seventeen patients (43.6%) had a partial response, 10 patients (25.6%) had stable disease, and 11 patients (28.2%) had progressive disease. A statistically significant difference was observed (P < .001) between the response to (90)Y-DOTATOC treatment and the response to biotherapy with somatostatin analogs and chemotherapy and also between the current results and the results from a previous similar study (P < .05). At the time of the current evaluation with ongoing follow-up for 30 patients, the median progression-free survival was 22.3 months. CONCLUSIONS: The results from this phase 2 study indicated that the treatment of metastatic neuroendocrine tumors with fixed (90)Y-DOTATOC activity is useful and safe.

Peptide Receptor Radionuclide Therapy (PRRT) in a Patient Affected by Metastatic Breast Cancer with Neuroendocrine Differentiation.

BACKGROUND: Breast cancer (BC) is the most frequent cancer in European women with nearly 30% of the patients eventually developing metastases. Neuroendocrine differentiation is a rare event, but overexpression of somatostatin receptors in BC has been reported in many studies. CASE REPORT: A patient with liver metastases from BC was treated with peptide receptor radionuclide therapy (PRRT). Computed tomography scan and biochemical examinations showed a clear response to radionuclide therapy. CONCLUSION: PRRT may be useful in metastatic BC patients.