Targeted radiation therapy (TRT) is a strategy increasingly adopted for the treatment of different types of cancer. The urge for optimization, as stated by the European Council Directive (2013/59/EURATOM), requires the implementation of a personalized dosimetric approach, similar to what already happens in external beam radiation therapy (EBRT). The purpose of this paper is to provide a thorough introduction to the field of personalized dosimetry in TRT, explaining its rationale in the context of optimization and describing the currently available methodologies. After listing the main therapies currently employed, the clinical workflow for the absorbed dose calculation is described, based on works of the most experienced authors in the literature and recent guidelines. Moreover, the widespread software packages for internal dosimetry are presented and critical aspects discussed. Overall, a selection of the most important and recent articles about this topic is provided.

Background: Dosimetry after radiopharmaceutical therapy with ¹⁷⁷Lu (¹⁷⁷Lu-RPT) relies on quantitative SPECT/CT imaging, for which suitable reconstruction protocols are required. In this study, we characterized for the first time the quantitative performance of a ring-shaped CZT-based camera using two different reconstruction algorithms: an ordered subset expectation maximization (OSEM) and a block sequential regularized expectation maximization (BSREM) combined with noise reduction regularization. This study lays the foundations for the definition of a reconstruction protocol enabling accurate dosimetry for patients treated with ¹⁷⁷Lu-RPT. Methods: A series of ¹⁷⁷Lu-filled phantoms were acquired on a StarGuide™ (GE HealthCare), with energy and scatter windows centred at 208 (± 6%) keV and 185 (± 5%) keV, respectively. Images were reconstructed with the manufacturer implementations of OSEM (GE-OSEM) and BSREM (Q.Clear) algorithms, and various combinations of iterations and subsets. Additionally, the manufacturer-recommended Q.Clear-based reconstruction protocol was evaluated. Quantification accuracy, measured as the difference between the SPECT-based and the radionuclide calibrator-based activity, and noise were evaluated in a large cylinder. Recovery coefficients (RCs) and spatial resolution were assessed in a NEMA IEC phantom with sphere inserts. The reconstruction protocols considered suitable for clinical applications were tested on a cohort of patients treated with [¹⁷⁷Lu]Lu-PSMA-I&T. Results: The accuracy of the activity from the cylinder, although affected by septal penetration, was < 10% for all reconstructions. Both algorithms featured improved spatial resolution and higher RCs with increasing updates at the cost of noise build-up, but Q.Clear outperformed GE-OSEM in reducing noise accumulation. When the reconstruction parameters were carefully selected, similar values for noise (~0.15), spatial resolution (~1 cm) and RCs were found, irrespective of the reconstruction algorithm. Analogue results were found in patients. Conclusions: Accurate activity quantification is possible when imaging ¹⁷⁷Lu with StarGuide™. However, the impact of septal penetration requires further investigations. GE-OSEM is a valid alternative to the recommended Q.Clear reconstruction algorithm, featuring comparable performances assessed on phantoms and patients.

Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-TATE has emerged as a promising treatment for gastroenteropancreatic neuroendocrine tumours (GEP-NETs). Its treatment protocol is currently standardised for all patients, resulting in different patient outcomes. This study investigates the variability of tumours and organs-at-risk (kidneys and red marrow) dosimetric parameters across treatment cycles in patients with pancreatic and intestinal NETs. Data from 37 patients enrolled in a prospective phase II study (LuMEn) were analysed. Treatment consisted of four cycles of [177Lu]Lu-DOTA-TATE administered 8–12 weeks apart. Three-time-point SPECT/CT imaging was performed after each treatment cycle, and dosimetry of tumours and organs-at-risk (kidneys and red marrow) was conducted following the medical internal radiation dose formalism. Coefficients of variation (CoV) assessed the variability of absorbed doses, activity concentrations on day 1, and effective half-lives. Linear mixed effect models (SAS software) were used to investigate the evolution of the dosimetric parameters over cycles, discerning between different primary NET types and grades of tumours. There is an important variability in absorbed doses and activity concentrations among patients, particularly in tumours (CoV: ~50%). Tumour absorbed doses and activity concentrations decreased over treatment cycles in pancreatic NETs, although at a limited rate (~-13%/cycle). An opposite trend was observed for the kidneys ( ~ + 8%/cycle). Effective half-lives remained relatively constant across cycles for both organs-at-risk and tumours. The primary NET type significantly influenced effective half-lives in tumours, shorter in pancreatic NETs than intestinal NETs (77 h vs. 107 h, p < 0.0001). No significant effect of the grade was observed on either of the variables investigated. Our study revealed considerable variations in tumour absorbed doses among patients with NETs treated with a standardized protocol. These findings confirm the need for personalized dosimetry approaches in PRRT, considering patient and tumour characteristics. EudraCT Number: 2012-003666-41. Clinicaltrials.gov identifier: NCT01842165. Registered 25 April 2013, https://clinicaltrials.gov/ct2/show/NCT01842165 .

Purpose: Following the clinical success of $$^{177}\text{Lu}$$ -based therapies for neuroendocrine tumors and prostate cancer, accurate quantification of $$^{177}\text{Lu}$$ using radionuclide calibrators (RNCs) and SPECT/CT is gaining importance as prerequisite for accurate treatment delivery and dosimetry. However, the lack of standardization can introduce inter-system variability, compromising multi-center clinical trials. This study aimed to assess the accuracy and variability of $$^{177}\text{Lu}$$ measurements using RNCs and SPECT/CT across different systems and hospitals. Methods: A uniform cylindrical phantom and a NEMA phantom with hot spheres were prepared using traceable activities and imaged at 8 different hospitals using 13 SPECT/CT systems (9 conventional and 4 3D CZT). Acquisitions and reconstructions were performed using both site-specific and standardized protocols. The cylindrical phantom images were used to evaluate the system calibration and establish image calibration factors (ICFs), the NEMA images to evaluate effective resolution by calculating recovery coefficients (RCs). In parallel, two vials were measured to test RNC accuracy. Results: RNC measurements differed up to 11% between centers, while SPECT quantification of the cylindrical phantom differed up to 20%. While ICFs were consistent for systems of the same type, image quality varied strongly when using clinical protocols (36% difference in RCs in the largest sphere). Standardized reconstruction reduced variability in RCs for each system type (maximum 12% difference), regardless of acquisition protocol, but differences between system types persisted when standardizing acquisition and reconstruction (33% difference). Conclusion: Current $$^{177}\text{Lu}$$ measurement practices yield significant variability in quantification and image quality. Harmonization efforts should prioritize standardized calibration and reconstruction protocols to improve multicenter reproducibility of quantitative $$^{177}\text{Lu}$$ -SPECT/CT.

Ring-shaped systems based on CZT are promising for quantitative imaging, but their accuracy may be affected by septal penetration of high-energy photons-given the fixed collimator-and by limitations in scatter correction due to low-energy tailing. This study compares the quantitative performance of a ring-shaped CZT system with that of a conventional dual-head NaI SPECT/CT system (StarGuide™ and NM/CT 870 DR, both GE HealthCare) using the 208 keV photopeak of ¹⁷⁷Lu. A NEMA phantom with 3D-printed anthropomorphic inserts, including kidneys and lumbar vertebrae, as well as standard spherical inserts, was filled with activity concentrations mimicking the distribution observed in patients 1 day post-injection of 7.4 GBq of [¹⁷⁷Lu]Lu-PSMA-I&T. The phantom was scanned repeatedly on both systems (scan duration/bed position: 7 min for StarGuide™ and 20 min for NM/CT 870 DR). Quantitative accuracy and reproducibility were evaluated using the mean error and the coefficient of variation (CV) over repeated measurements, respectively. Additionally, a group of patients treated with [¹⁷⁷Lu]Lu-PSMA-I&T underwent sequential SPECT/CT on both systems to confirm the phantom-based results. The total activity measured within the phantom deviated from the expected value by means of 13% for the StarGuide™ and 0% for the NM/CT 870 DR. After partial-volume-effect correction based on recovery coefficients, the activity concentration in kidney inserts was measured with ~ 5% accuracy on both systems. For the StarGuide™, mean errors in tumour inserts (volumes: 2.6-28 ml) ranged from - 8% to 3%, whereas a consistent underestimation by an average of - 11% was observed for the NM/CT 870 DR. The StarGuide™ significantly overestimated the background activity concentration (59%), while the NM/CT 870 DR showed a smaller error (- 8%). Reproducibility was lower for the StarGuide™, with maximum CV values of 7%, compared with 3% for the NM/CT 870 DR. Clinical findings were consistent with phantom results. The StarGuide™ provided slightly more accurate activity quantification in regions of high relative uptake, such as tumours and kidneys, compared with the NM/CT 870 DR. However, quantification in regions of low relative uptake and total activity estimation were less accurate, likely due to septal penetration. The lower reproducibility suggests that longer scan durations may be considered.