Purpose: A multidisciplinary expert panel convened to formulate state-of-the-art recommendations for optimisation of selective internal radiation therapy (SIRT) with yttrium-90 (⁹⁰Y)-resin microspheres. Methods: A steering committee of 23 international experts representing all participating specialties formulated recommendations for SIRT with ⁹⁰Y-resin microspheres activity prescription and post-treatment dosimetry, based on literature searches and the responses to a 61-question survey that was completed by 43 leading experts (including the steering committee members). The survey was validated by the steering committee and completed anonymously. In a face-to-face meeting, the results of the survey were presented and discussed. Recommendations were derived and level of agreement defined (strong agreement ≥ 80%, moderate agreement 50%–79%, no agreement ≤ 49%). Results: Forty-seven recommendations were established, including guidance such as a multidisciplinary team should define treatment strategy and therapeutic intent (strong agreement); 3D imaging with CT and an angiography with cone-beam-CT, if available, and ^99mTc-MAA SPECT/CT are recommended for extrahepatic/intrahepatic deposition assessment, treatment field definition and calculation of the ⁹⁰Y-resin microspheres activity needed (moderate/strong agreement). A personalised approach, using dosimetry (partition model and/or voxel-based) is recommended for activity prescription, when either whole liver or selective, non-ablative or ablative SIRT is planned (strong agreement). A mean absorbed dose to non-tumoural liver of 40 Gy or less is considered safe (strong agreement). A minimum mean target-absorbed dose to tumour of 100–120 Gy is recommended for hepatocellular carcinoma, liver metastatic colorectal cancer and cholangiocarcinoma (moderate/strong agreement). Post-SIRT imaging for treatment verification with ⁹⁰Y-PET/CT is recommended (strong agreement). Post-SIRT dosimetry is also recommended (strong agreement). Conclusion: Practitioners are encouraged to work towards adoption of these recommendations.

The main challenge for systemic radiation therapy using radiopharmaceuticals (SRT) is to optimise the dose delivered to the tumour, while minimising normal tissue irradiation. Dosimetry could help to increase therapy response and decrease toxicity after SRT by individual treatment planning. Peptide receptor radionuclide therapy (PRRT) is an accepted SRT treatment option for irresectable and metastatic neuroendocrine tumours (NET). However, dosimetry in PRRT is not routinely performed, mainly due to the lack of evidence in literature and clinical implementation difficulties. The goal of this review is to provide insight in dosimetry methods and requirements and to present an overview of clinical aspects of dosimetry in PRRT for NET. A PubMed query including the search criteria dosimetry, radiation dose, peptide receptor radionuclide therapy, and radionuclide therapy was performed. Articles were selected based on title and abstract, and description of dosimetric approach. A total of 288 original articles were included. The most important dosimetry methods, their main advantages and limitations, and implications in the clinical setting are discussed. An overview of dosimetry in clinical studies regarding PRRT treatment for NET is provided. Clinical dosimetry in PRRT is feasible and can result in improved treatment outcomes. Current clinical dosimetry studies focus on safety and apply non-voxel-based dosimetry methods. Personalised treatment using sophisticated dosimetry methods to assess tumour and normal tissue uptake in clinical trials is the next step towards routine dosimetry in PRRT for NET.

This study investigated the feasibility of quantitative accuracy and harmonized image quality in (89)Zr-PET/CT multicenter studies. Five PET/CT scanners from 3 vendors were included. (89)Zr activity was measured in a central dose calibrator before delivery. Local activity assays were based on volume as well as on the local dose calibrator. Accuracy and image noise were determined from a cross calibration experiment. Image quality was assessed from recovery coefficients derived from different volume-of-interest (VOI) methods (VOI A 50%, based on a 3-dimensional isocontour at 50% of the maximum voxel value with local background correction; VOI Max, based on the voxel with the highest uptake; and VOI 3Dpeak, based on a spheric VOI of 1.2-cm diameter positioned so as to maximize the enclosed average). PET images were analyzed before and after postreconstruction smoothing, applied to match image noise. PET/CT accuracy and image noise ranged from -3% to 10% and from 13% to 22%, respectively. VOI 3Dpeak produced the most reproducible recovery coefficients. After calibration of the local dose calibrator to the central dose calibrator, differences between the local activity assays were within 6%. This study showed that quantitative accuracy and harmonized image quality can be reached in (89)Zr PET/CT multicenter studies.

Background: Response after peptide receptor radionuclide therapy (PRRT) can be evaluated using anatomical imaging (CT/MRI), somatostatin receptor imaging ([⁶⁸Ga]Ga-DOTA-TATE PET/CT), and serum Chromogranin-A (CgA). The aim of this retrospective study is to assess the role of these response evaluation methods and their predictive value for overall survival (OS). Methods: Imaging and CgA levels were acquired prior to start of PRRT, and 3 and 9 months after completion. Tumour size was measured on anatomical imaging and response was categorized according to RECIST 1.1 and Choi criteria. [⁶⁸Ga]Ga-DOTA-TATE uptake was quantified in both target lesions depicted on anatomical imaging and separately identified PET target lesions, which were either followed over time or newly identified on each scan with PERCIST-based criteria. Response evaluation methods were compared with Cox regression analyses and Log Rank tests for association with OS. Results: A total of 44 patients were included, with median follow-up of 31 months (IQR 26–36 months) and median OS of 39 months (IQR 32mo-not reached)d. Progressive disease after 9 months (according to RECIST 1.1) was significantly associated with worse OS compared to stable disease [HR 9.04 (95% CI 2.10–38.85)], however not compared to patients with partial response. According to Choi criteria, progressive disease was also significantly associated with worse OS compared to stable disease [HR 6.10 (95% CI 1.38–27.05)] and compared to patients with partial response [HR 22.66 (95% CI 2.33–219.99)]. In some patients, new lesions were detected earlier with [⁶⁸Ga]Ga-DOTA-TATE PET/CT than with anatomical imaging. After 3 months, new lesions on [⁶⁸Ga]Ga-DOTA-TATE PET/CT which were not visible on anatomical imaging, were detected in 4/41 (10%) patients and in another 3/27 (11%) patients after 9 months. However, no associations between change in uptake on ⁶⁸Ga-DOTA-TATE PET/CT or serum CgA measurements and OS was observed. Conclusions: Progression on anatomical imaging performed 9 months after PRRT is associated with worse OS compared to stable disease or partial response. Although new lesions were detected earlier with [⁶⁸Ga]Ga-DOTA-TATE PET/CT than with anatomical imaging, [⁶⁸Ga]Ga-DOTA-TATE uptake, and serum CgA after PRRT were not predictive for OS in this cohort with limited number of patients and follow-up time.