Implementation of dosimetry for molecular radiotherapy; results from a European survey.

PURPOSE: The use of molecular radiotherapy (MRT) has been rapidly evolving over the last years. The aim of this study was to assess the current implementation of dosimetry for MRTs in Europe. METHODS: A web-based questionnaire was open for treating centres between April and June 2022, and focused on 2020-2022. Questions addressed the application of 16 different MRTs, the availability and involvement of medical physicists, software used, quality assurance, as well as the target regions for dosimetry, whether treatment planning and/or verification were performed, and the dosimetric methods used. RESULTS: A total of 173 responses suitable for analysis was received from centres performing MRT, geographically distributed over 27 European countries. Of these, 146 centres (84 %) indicated to perform some form of dosimetry, and 97 % of these centres had a medical physicist available and almost always involved in dosimetry. The most common MRTs were 131I-based treatments for thyroid diseases and thyroid cancer, and [223Ra]RaCl2 for bone metastases. The implementation of dosimetry varied widely between therapies, from almost all centres performing dosimetry-based planning for microsphere treatments to none for some of the less common treatments (like 32P sodium-phosphate for myeloproliferative disease and [89Sr]SrCl2 for bone metastases). CONCLUSIONS: Over the last years, implementation of dosimetry, both for pre-therapeutic treatment planning and post-therapy absorbed dose verification, increased for several treatments, especially for microsphere treatments. For other treatments that have moved from research to clinical routine, the use of dosimetry decreased in recent years. However, there are still large differences both across and within countries.

Impact of patient's habitus on image quality and quantitative metrics in 18F-FDG PET/CT images.

PURPOSE: To study how the quantitative parameters of 18F-FDG PET imaging change with the emission scan duration (ESD) and the body-mass-index (BMI) in phantom and patients on a time-of-flight (TOF)-PET/CT system. METHODS: The image-quality phantom with (b-NEMA-IQ, BMI = 29.2 kg/m2) and without (NEMA-IEC, BMI = 21.4 kg/m2) a 'belt' of water-bags was filled with 18F-FDG activities to obtain nominal standardized uptake values (SUV) of 19, 8 and 5. Patients with BMI ≤ 25 kg/m2 (L-BMI) and BMI > 25 kg/m2 (H-BMI) were enrolled in this study. Phantom and patients underwent list-mode PET acquisition at 120 s/bed-position. Images reconstructed with clinical protocol and different ESD (120, 90, 75, 60, 45, 30 s) were analysed for comparison of maximum SUV (SUVmax), maximum standardized uptake value lean-body-mass corrected (SULmax) and noise. RESULTS: 79 oncologic patients (45 L-BMI, 44 H-BMI) were analysed. From 90 s to 30 s, an increasing variation of SUVmax and SULmax with respect to the reference 120 s time was observed, from 18% to 60% and from 16% to 37% for phantom and patients, respectively. SUVmax values were significantly higher (+50%) in b-NEMA-IQ than NEMA-IQ phantom and in H-BMI (+33%) than L-BMI patients. No significant difference was found in SULmax for the two BMI categories in both phantom and patients. CV values decreased when increasing ESD, being higher in H-BMI patients (0.13-0.25) and b-NEMA-IQ phantom (0.15-0.28) than in L-BMI patients (0.11-0.21) and NEMA-IQ phantom (0.11-0.20). CONCLUSIONS: Reduction of ESD may severely impact on the variations of SUVmax and SULmax in 18F-FDG PET/CT imaging. This study confirms recommendations of using SUL for lesion uptake quantification, being unaffected by BMI variation.

Dosimetric optimization of nuclear medicine therapy based on the Council Directive 2013/59/EURATOM and the Italian law N. 101/2020. Position paper and recommendations by the Italian National Associations of Medical Physics (AIFM) and Nuclear Medicine (AIMN).

This recommendation by the Italian Associations of Nuclear Medicine (AIMN) and Medical Physics (AIFM) focuses on the dosimetric optimization of Nuclear Medicine Therapy (NMT) as clearly requested by the article 56 of the EURATOM Directive 2013/59 and its consequent implementation in article 158 in the Italian Law n. 101/2020. However, this statement must deal with scientific and methodological limits that still exist and, above all, with the currently available limited resources. This paper addresses these specific issues. It distinguishes among many possible kinds of NMT. For each type, dosimetric optimization is recommended or considered optional, according to the general criteria adopted in any human choice, i.e. a check of technical feasibility first, followed by a cost/benefit argument. The classification of therapies as standardized or non-standardized is presented. This is based on the complexity of the type of pathology, on the variability of the treatment outcome, and on the risks involved. According to the present document, which was officially delivered to Italian Health Ministry as necessary interpretation of the law, a therapeutic team can, in science and consciousness, overcome the indications of posology, to optimize and tailoring a treatment with dosimetry, on the basis of published national or international data or guidelines, without need of an Ethics Committee approval. Data collected in this way will provide additional evidence about optimal dosimetric reference values. As conclusion, a formal appeal is made to the European and National regulatory agencies for pharmaceuticals to obtain the official acknowledgment of this principle.

Downstaging unresectable hepatocellular carcinoma by radioembolization using 90-yttrium resin microspheres: a single center experience.

BACKGROUND: Only one third of patients with hepatocellular carcinoma can benefit from curative treatments at the time of first diagnosis. Tumor downstaging by radioembolization may enable initially unresectable hepatocellular carcinoma (HCC) to be treated with surgery lengthening survival. METHODS: From June 2011 through June 2014, all patients with a first diagnosis of unresectable HCC with intrahepatic portal vein thrombosis were treated in our center with radioembolization using 90-yttrium resin microspheres. A 3-year enrollment period and a 5-year follow-up were planned to adequately investigate survivals. RESULTS: Twenty-four patients were enrolled, five were downstaged to surgery, eight did not reach downstaging but achieved partial response or stable disease, and eleven showed HCC progression despite radioembolization. High tumor absorbed radiation doses (454 vs. 248 and 138 Gy, P=0.005) and low serum AFP levels (53 vs. 1,447 and 4,603 ng/mL, P=0.05) were the variables significantly associated with successful downstaging. Mean and median survivals were 54, 30 and 11 months and 70, 24 and 11 months in the three groups respectively. No severe side effects were registered. CONCLUSIONS: In our center, about 20% of patients with locally advanced unresectable hepatocellular carcinoma were successfully downstaged to surgery after radioembolization. This strategy increases survival and is associated with an excellent safety profile.

Performance evaluation of a new time of flight PET/CT scanner: Results of a multicenter study.

PURPOSE: The aim of this multicenter study was to evaluate the performance of the upgraded version of the Ingenuity TF PET/CT scanner, according to the NEMA NU-2 2012 standards. METHODS: Spatial resolution, sensitivity, count rate response, scatter fraction, image quality and accuracy were evaluated on three Ingenuity TF scanners installed in Italian hospitals. Furthermore, energy and timing resolution were measured. A detailed image quality phantom analysis was performed to evaluate the effect of different clinical reconstruction parameters, including the application of PSF correction. RESULTS: Results show an average spatial resolution of 4.7 mm and an average absolute system sensitivity of 7.9 cps/kBq. The average maximum NECR was 119.83 kcps at 20.67 kBq/ml, while the maximum true event rate was 322.62 kcps at the concentration of 24.51 kBq/ml. The average maximum bias below NECR peak was 12.58%. All the results of NEMA tests were in agreement with the values declared by the manufacturer. The estimated average energy and timing resolution were 10.83% and 536.2 ps, respectively. Image quality phantom analysis obtained with different reconstruction settings showed that PSF correction was the parameter that affected mainly on contrast recovery coefficient, while the iteration number and amplitude of Gaussian filter had no significant effect. Of relevance, the application of PSF correction never led to recovery coefficient values higher than 100% and to Gibbs or edge artifacts. CONCLUSIONS: The new Ingenuity TF model shows physical performance similar to other scanners of the latest generation for all standard NEMA NU2-2012 measurements.

PET-CT post therapy dosimetry in radioembolization with resin 90Y microspheres: Comparison with pre-treatment SPECT-CT 99mTc-MAA results.

Resin microspheres radioembolization is an effective treatment for liver tumors when the surgical option is not feasible. Doses delivered to tumor and normal liver can be assess in the pre-therapy phase by means of a 99mTc-MAA SPECT-CT simulation and after the treatment with 90Y PET-CT acquisition. The optimal therapeutic 90Y activity is determined on 99mTc-MAA SPECT-CT dose results in order to avoid healthy parenchyma toxicity and to effectively irradiate the tumor. The assumption of identical radiopharmaceutical distribution between simulation and verification is still under debate and literature data showed controversial results. In this study 10 HCC patient's dosimetry performed on 99mTc SPECT-CT and 90Y PET-CT were compared. Patients were selected when a good agreement between the pre and post-therapy distribution was observed in order to investigate the intrinsic dosimetric variations between the two imaging modalities. Mean doses (MIRD and Voxel approaches) showed a good correlation (Pearson's coefficient r > 0.90) both for tumor and normal liver. Dose Volume Histogram curves were compared with a good agreement particularly for normal liver (D50). Goal doses were achieved for 90% of patients. Bland-Altman analysis indicates lower variations for healthy parenchyma than for tumor (1.96 SD equal to 9.1 Gy and 68 Gy respectively) confirming the robustness of the dose-toxicity approach. PET-CT dosimetry well correlates with SPECT-CT doses (under assumption of same catheter position and 90Y activity). Better agreement was showed for 7/10 and 8/10 patients for T and NL respectively, confirming dosimetry as effective tool to optimize and individualize the treatment.

Calculation of tumour and normal tissue biological effective dose in 90Y liver radioembolization with different dosimetric methods.

PURPOSE: Radioembolization with 90Y microspheres is an effective treatment for unresectable liver tumours. Two types of microspheres are available: resin (SIR-Spheres®) and glass (Theraspheres®). The aim of this study is to compare biological effective dose (BED) values obtained with three different dosimetric methods. METHODS: 29 HCC patients were included in this study: 15 were treated with resin(mean injected activity 1.5GBq, range 0.8-2.7GBq) and 14 with glass microspheres (2.6GBq, range 1.3-4.1GBq). Average doses to tumours and normal liver tissues were calculated with AAPM, multi-compartmental MIRD and Voxel-based methods and consequently the BED values were obtained. Planar images were used for the AAPM method: 99mTc-MAA SPECT-CT attenuation and scatter corrected images (resin) and 99m Tc-MAA SPECT attenuation corrected (glass) were employed for the other two methods. RESULTS: Regardless of type of microspheres, both for tumours and normal liver tissues, no significant statistical differences were found between MIRD and Voxel for both doses and BED values. Conversely AAPM gave discordant results with respect to the other two methods (Mann-Whitney p-values⩽0.01). For resin spheres the calculated tumour-to-normal tissue ratios on planar images were on average 14 times greater than those obtained on SPECT-CT images, while they were 4 times greater on glass. A linear correlation was observed between MIRD and Voxel BEDs. CONCLUSIONS: The AAPM method appears to be less precise for absorbed dose and BED estimation, while MIRD and voxel based dosimetry are more confident each other.