Peptide receptor radionuclide therapy with 177Lu-DOTATATE has become a standard treatment modality in neuroendocrine tumours (NETs). No consensus has yet been reached however regarding the absorbed dose threshold for lesion response, the absorbed dose limit to organs-at-risk, and the optimal fractionation and activity to be administered. This is partly due to a lack of uniform and comparable dosimetry protocols. The present article details the development of an organ-at-risk dosimetry procedure, which could be implemented and used routinely in a clinical context. Forty-seven patients with NETs underwent 177Lu-DOTATATE therapy. Three SPECT/CT images were acquired at 4, 24 and 144-192 h post-injection. Three blood samples were obtained together with the SPECT/CT acquisitions and 2 additional samples were obtained around 30 min and 1 h post-injection. A bi-exponential fit was used to compute the source organ time-integrated activity coefficients. Coefficients were introduced into OLINDA/EXM software to compute organ-at-risk absorbed doses. Median values for all patients were computed for absorbed dose coefficient D/A0 and for late effective half-life T1/2eff for kidneys, spleen and red marrow. Dosimetry resulted in a median[interquartile range] of 0.78[0.35], 1.07[0.58] and 0.028[0.010] Gy/GBq for D/A0 and of 55[9], 71[9] and 52[18] h for T1/2eff for kidneys, spleen and red marrow respectively. A dosimetry procedure for organs-at-risk in 177Lu-DOTATATE therapy based on serial SPECT/CT images and blood samples can be implemented routinely in a clinical context with limited patient burden. The results obtained were in accordance with those of other centres.

Https://doi.org/10.18632/oncotarget.27460 Ioannis Karfis, Gwennaëlle Marin, Hugo Levillain, Stylianos Drisis, Raoul Muteganya, Gabriela Critchi, Loubna Taraji-Schiltz, Carlos Artigas Guix, Leila...

In order to obtain a reliable 177Lu-DOTATATE therapy dosimetry, it is crucial to acquire accurate and precise activity measurements with the radionuclide calibrator, the SPECT/CT camera, and the NaI(Tl) well counter. The aim of this study was to determine, in a clinical context, the accuracy and the precision of their activity quantification over a range of activities and time. Ninety-three 177Lu sources from the manufacturer were measured in the radionuclide calibrator over 2.5 years to evaluate its calibration accuracy and precision compared to the manufacturer’s value. A NEMA 2012/IEC 2008 phantom was filled with a 177Lu activity concentration sphere-to-background ratio of five. It was acquired with the SPECT/CT camera to determine the reconstruction parameters offering the best compromise between partial volume effect and signal-to-noise ratio. The calibration factor was computed accordingly. The calibration quality was monitored over 2.5 years with 33 phantom acquisitions with activities ranging from 7040 to 0.6 MBq. Home-made sources were used to calibrate the well counter. Its reliability was evaluated with activities ranging from 150 to 0.2 kBq measured 34 times over 2.5 years. For the radionuclide calibrator, median [interquartile range] for the error on activity measurement was −0.99 [1.31] %. The optimal SPECT reconstruction parameters were obtained with 16 iterations, 16 subsets and a 12-mm Gaussian post-filter. The calibration factor was 9.87 cps/MBq with an error of −1.05 [2.12] %. The well counter was calibrated with 31.5 cps/kBq, and the error was evaluated to −12.89 [16.55] %. The accuracy and the precision of activity quantification using dedicated quality control were found to be sufficient for use in dosimetry implemented in clinical routine. The proposed methodology could be implemented in other centres to obtain reproducible 177Lu-based treatment dosimetry.

A 51-year-old male was found with bilateral thyroid nodules on ultrasonography neck imaging. The largest nodule, measuring 23 × 26 × 35 mm, was located in the left lobe and was classified as EU-TIRADS 4. Thyroid function tests were normal, as were serum levels of parathormone, Chromogranin A, carcinoembryonic antigen and calcitonin. The nodule was cold on thyroid scintigraphy. Fine-needle aspiration of the nodule did not demonstrate cellular atypia. High focal uptake was found on both ¹¹¹In-DTPA-octreotide scintigraphy and ⁶⁸Ga-DOTATATE PET/CT. Histopathological analysis showed a microfollicular adenoma without malignancy. Immunohistochemical staining did not suggest neuroendocrine neoplasia or C cell hyperplasia. However, high expression of somatostatin receptor 2 (SSTR2) was observed in the microfollicular adenoma compared to the surrounding healthy tissue, with predominant localization in the endothelial cells and at the secretory pole of the thyroid epithelial cells in contact with blood vessels. High focal thyroid uptake on ⁶⁸Ga-DOTATATE PET/CT can be observed in benign thyroid nodules due to an overexpression of SSTR by endothelial cells. However, incidental focal thyroid uptake on SSTR imaging requires further investigations to rule out thyroid malignancy.