Quality Assurance Considerations in Radiopharmaceutical Therapy Dosimetry Using PLANETDose: An International Atomic Energy Agency Study.

Implementation of radiopharmaceutical therapy dosimetry varies depending on the clinical application, dosimetry protocol, software, and ultimately the operator. Assessing clinical dosimetry accuracy and precision is therefore a challenging task. This work emphasizes some pitfalls encountered during a structured analysis, performed on a single-patient dataset consisting of SPECT/CT images by various participants using a standard protocol and clinically approved commercial software. Methods: The clinical dataset consisted of the dosimetric study of a patient administered with [177Lu]Lu-DOTATATE at Tygerberg Hospital, South Africa, as a part of International Atomic Energy Agency-coordinated research project E23005. SPECT/CT images were acquired at 5 time points postinjection. Patient and calibration images were reconstructed on a workstation, and a calibration factor of 122.6 Bq/count was derived independently and provided to the participants. A standard dosimetric protocol was defined, and PLANETDose (version 3.1.1) software was installed at 9 centers to perform the dosimetry of 3 treatment cycles. The protocol included rigid image registration, segmentation (semimanual for organs, activity threshold for tumors), and dose voxel kernel convolution of activity followed by absorbed dose (AD) rate integration to obtain the ADs. Iterations of the protocol were performed by participants individually and within collective training, the results of which were analyzed for dosimetric variability, as well as for quality assurance and error analysis. Intermediary checkpoints were developed to understand possible sources of variation and to differentiate user error from legitimate user variability. Results: Initial dosimetric results for organs (liver and kidneys) and lesions showed considerable interoperator variability. Not only was the generation of intermediate checkpoints such as total counts, volumes, and activity required, but also activity-to-count ratio, activity concentration, and AD rate-to-activity concentration ratio to determine the source of variability. Conclusion: When the same patient dataset was analyzed using the same dosimetry procedure and software, significant disparities were observed in the results despite multiple sessions of training and feedback. Variations due to human error could be minimized or avoided by performing intensive training sessions, establishing intermediate checkpoints, conducting sanity checks, and cross-validating results across physicists or with standardized datasets. This finding promotes the development of quality assurance in clinical dosimetry.

Acute Toxicity and Quality of Life in a Post-Prostatectomy Ablative Radiation Therapy (POPART) Multicentric Trial.

BACKGROUND: The aim of this study was to investigate the feasibility of ultrahypofractionated radiotherapy to the prostate bed in patients with biochemical and/or clinical relapse following radical prostatectomy who were enrolled in the prospective, observational, multicentric POPART trial (NCT04831970). METHODS: Patients with post-radical prostatectomy PSA levels of ≥0.1-2.0 ng/mL and/or local relapse at PSMA PET/CT or multiparametric MRI were treated with Linac-based SBRT on the prostate bed up to a total dose of 32.5 Gy in five fractions every other day (EQD21.5 = 74.2 Gy). Maximum acute toxicity was assessed using the Common Terminology Criteria for Adverse Events version 5 scale. International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) scores were assessed at baseline and during the follow-up. RESULTS: From April 2021 to June 2022, thirty men with a median age of 72 years (range 55-82) were enrolled in three centers. The median PSA level before RT was 0.30 ng/mL (range 0.18-1.89 ng/mL). At 3 months post-treatment, no GI or ≥2 GU side effects were reported; three patients (10%) experienced Grade 1 GU toxicity. No changes in ICIQ-SF or in the urinary domains of EPIC-CP were observed, while a transient worsening was registered in the bowel domain. At the same time point, all but two patients, who progressed distantly, were found to be biochemically controlled with a median post-treatment PSA level of 0.07 ng/mL (range 0-0.48 ng/mL). CONCLUSIONS: Our preliminary findings show that SBRT can be safely extended to the postoperative setting, without an increase in short-term toxicity or a significant decline in QoL. Long-term results are needed to confirm this strategy.

Developing and Implementing an Imaging Optimization Study in Pediatric Nuclear Medicine: Experience and Recommendations from an IAEA-Coordinated Research Project.

The International Atomic Energy Agency instituted a coordinated research project on the evaluation and optimization of pediatric imaging, addressing the lack of consistency in this field. The purpose was to develop and test an optimization schema for the practices of pediatric radiology and nuclear medicine. Methods: A 5-step optimization schema was developed. Once a protocol optimization is identified, the steps are as follows: identification of the imaging situation; collection of administered-activity data and evaluation of the diagnostic image quality at baseline; comparison of baseline administered activity data with published standards or other benchmarks; identification of intervention, if necessary; and implementation of intervention and evaluation. Results: Within the coordinated research project, two sites considered optimization projects regarding nuclear medicine. In this work, renal imaging using 99mTc-dimercaptosuccinic acid (DMSA) projects are presented as examples. Site 1 acquired its standard 300-s static 99mTc-DMSA studies as 5-frame dynamic studies in 29 children. Frames were added to simulate different levels of administered activity. Image quality was subjectively judged on a 3-point Likert scale. A 30% reduction in administered activity with increased imaging duration (350 s) across all age groups was shown to be acceptable. This reduction was implemented and evaluated in 31 subsequent children, yielding administered activities significantly lower than baseline (mean relative differences of 30%, 37%, and 38% for children aged 0-5, 5-10, and 10-15 y, respectively). Site 2 performed a phantom study to determine the impact of lowering administered activity on image noise, finding that administered activities could be significantly lowered if longer imaging times were used. This led to a 50%-70% reduction from baseline with no loss in image quality. Conclusion: A dose optimization approach was applied successfully for several procedures commonly performed in pediatric nuclear medicine. Results are reported for renal cortical imaging using 99mTc-DMSA, leading to significant reductions in administered activity (and thus radiation dose). This optimization schema can be successfully implemented by nuclear medicine clinics seeking to improve their approach to imaging children.

Oral health-related quality of life and clinical outcomes of immediately or delayed loaded implants in the rehabilitation of edentulous jaws: a retrospective comparative study.

BACKGROUND: Patient-centered outcomes are being given great attention by the dental scientific community. The Oral Health Impact Profile -14 questionnaire (OHIP-14) has been introduced to address patients' success criteria when describing the impact of oral rehabilitations on quality of life (OHrQoL). METHODS: Thirty-five patients wearing a full-arch implant-prosthesis being in place between 4 and 6 years before this analysis were considered eligible and then enrolled in the present retrospective study. According to their prosthetic anamnesis, two groups were defined: delayed loading group (IL-group) and immediate loading group (IL-group). At the moment of analysis, clinical and radiographic parameters were collected, and patients were asked to complete the Oral Health Impact Profile -14 questionnaire (OHIP-14) in order to measure their OHrQoL. RESULTS: Independent t-test showed total OHIP-14 scores to be not significantly different between groups; however, the domains "functional limitation" and "physical disability" resulted significantly higher in patients within the DL-group. On the contrary, social disability was higher in the IL-group. When the comparison was performed taking sex into account, no significant differences between groups were highlighted. Instead, the stratification for years of follow-up led to significant evidences. When the follow-up was shorter (less-than-5 years), the functional limitation reported scores were higher. CONCLUSIONS: Within the limitations of this study, the analysis supports the absence of significant differences between immediate loading and delayed loading full-arch protocol in term of clinical, radiological parameters and OHrQoL.

The IAEA Radiotracer Biodistribution Template - A community resource for supporting the standardization and reporting of radionuclide pre-dosimetry data.

Radionuclide absorbed-dose dosimetry is an active area of development and has the potential to positively impact molecular radiotherapies. At present, many of the operations required to perform dosimetry calculations are unstandardized and unestablished. While the current methodology allows reasonable dosimetry estimates to be derived and published, it can be difficult to understand, and reproduce, each others' work. To help alleviate this we have identified the collection of biodistribution information as a key step in all internal dosimetry calculations, and present a template that can be used to standardize its documentation and reporting. A generalized biodistribution template entitled the IAEA Radiotracer Biodistribution Template (IAEA RaBiT) has been built and distributed for users performing biodistribution measurements in the community. The template enables robust recording of dosimetry-relevant information through standardization of details and their format. It has been designed to be simple and easy to use, and establish a structured recording of a common reference point in dosimetry operations - biodistribution data documentation. Improved documentation procedures may benefit organization of in house data, or be used to disseminate details throughout the community - for example to supplement dosimetry related publications. The standard format information may also enable the creation of new dosimetry related tools and protocols and support robust population databases. As dosimetry in nuclear medicine becomes more routinely applied in clinical applications, we need to develop the infrastructure for robustly handling large amounts of these data. Our IAEA RaBiT can be used as a standard format structure for data collection, organization, and dissemination.

Multi-centre evaluation of accuracy and reproducibility of planar and SPECT image quantification: An IAEA phantom study.

Accurate quantitation of activity provides the basis for internal dosimetry of targeted radionuclide therapies. This study investigated quantitative imaging capabilities at sites with a variety of experience and equipment and assessed levels of errors in activity quantitation in Single-Photon Emission Computed Tomography (SPECT) and planar imaging. Participants from 9 countries took part in a comparison in which planar, SPECT and SPECT with X ray computed tomography (SPECT-CT) imaging were used to quantify activities of four epoxy-filled cylinders containing 133Ba, which was chosen as a surrogate for 131I. The sources, with nominal volumes of 2, 4, 6 and 23mL, were calibrated for 133Ba activity by the National Institute of Standards and Technology, but the activity was initially unknown to the participants. Imaging was performed in a cylindrical phantom filled with water. Two trials were carried out in which the participants first estimated the activities using their local standard protocols, and then repeated the measurements using a standardized acquisition and analysis protocol. Finally, processing of the imaging data from the second trial was repeated by a single centre using a fixed protocol. In the first trial, the activities were underestimated by about 15% with planar imaging. SPECT with Chang's first order attenuation correction (Chang-AC) and SPECT-CT overestimated the activity by about 10%. The second trial showed moderate improvements in accuracy and variability. Planar imaging was subject to methodological errors, e.g., in the use of a transmission scan for attenuation correction. The use of Chang-AC was subject to variability from the definition of phantom contours. The project demonstrated the need for training and standardized protocols to achieve good levels of quantitative accuracy and precision in a multicentre setting. Absolute quantification of simple objects with no background was possible with the strictest protocol to about 6% with planar imaging and SPECT (with Chang-AC) and within 2% for SPECT-CT.

Radretumab radioimmunotherapy in patients with brain metastasis: a 124I-L19SIP dosimetric PET study.

Radioimmunotherapy (RIT) with (131)I-labeled L19SIP (radretumab; a small immunoprotein format antibody directed against the ED-B domain of fibronectin; ∼ 80 kDa molecular weight) has been investigated in several clinical trials. Here, we describe the use of immuno-PET imaging with iodine-124 ((124)I)-labeled L19SIP to predict doses delivered to tumor lesions and healthy organs by a subsequent radretumab RIT in patients with brain metastases from solid cancer. Bone marrow doses were evaluated both during the diagnostic phase and posttherapy, measuring activities in blood (germanium detector) and whole body (lanthanum bromide detector). Expected doses for radretumab administration (4,107 MBq/m(2)) were calculated from data obtained after administration of an average of 167 MBq (124)I-L19SIP to 6 patients. To assess lesion average doses, the positron emission tomography (PET) scanner was calibrated for the use of (124)I with an International Electrotechnical Commission (IEC) Body Phantom and recovery coefficients were calculated. The average dose to bone red marrow was 0.21 Gy/GBq, with high correlation between provisional and actual posttherapy doses. Although the fraction of injected activity in normal organs was similar in different patients, the antibody uptake in the neoplastic lesions varied by as much as a factor of 60. Immuno-PET with (124)I-labeled L19SIP offers significant advantages over conventional (131)I imaging, in particular accuracy of dosimetric results. Furthermore, the study indicates that antibody uptake can be highly variable even in different lesions of the same patient and that immuno-PET procedures may guide product development with armed antibodies.