A step toward simplified dosimetry of radiopharmaceutical therapy via SPECT frame duration reduction.

Despite being time-consuming, SPECT/CT data is necessary for accurate dosimetry in patient-specific radiopharmaceutical therapy. We investigated how reducing the frame duration (FD) during SPECT acquisition can simplify the dosimetry workflow for [177Lu]Lu-PSMA radioligand therapy (RLT). We aimed to determine the impact of shortened acquisition times on dosimetric precision. Three SPECT scans with FD of 20, 10, and 5 second/frame (sec/fr) were obtained 48 h post-RLT from one metastatic castration-resistant prostate cancer (mCRPC) patient's pelvis. Planar images at 4, 48, and 72 h post-therapy were used to calculate time-integrated activities (TIAs). Using accurate activity calibrations and GATE Monte Carlo (MC) dosimetry, absorbed doses in tumor lesions and kidneys were estimated. Dosimetry precision was assessed by comparing shorter FD results to the 20 sec/fr reference using relative percentage difference (RPD). We observed consistent calibration factors (CFs) across different FDs. Using the same CF, we obtained marginal RPD deviations less than 4% for the right kidney and tumor lesions and less than 7% for the left kidney. By reducing FD, simulation time was slightly decreased. This study shows we can shorten SPECT acquisition time in RLT dosimetry by reducing FD without sacrificing dosimetry accuracy. These findings pave the way for streamlined personalized internal dosimetry workflows.

Automated segmentation of lesions and organs at risk on [68Ga]Ga-PSMA-11 PET/CT images using self-supervised learning with Swin UNETR.

BACKGROUND: Prostate-specific membrane antigen (PSMA) PET/CT imaging is widely used for quantitative image analysis, especially in radioligand therapy (RLT) for metastatic castration-resistant prostate cancer (mCRPC). Unknown features influencing PSMA biodistribution can be explored by analyzing segmented organs at risk (OAR) and lesions. Manual segmentation is time-consuming and labor-intensive, so automated segmentation methods are desirable. Training deep-learning segmentation models is challenging due to the scarcity of high-quality annotated images. Addressing this, we developed shifted windows UNEt TRansformers (Swin UNETR) for fully automated segmentation. Within a self-supervised framework, the model's encoder was pre-trained on unlabeled data. The entire model was fine-tuned, including its decoder, using labeled data. METHODS: In this work, 752 whole-body [68Ga]Ga-PSMA-11 PET/CT images were collected from two centers. For self-supervised model pre-training, 652 unlabeled images were employed. The remaining 100 images were manually labeled for supervised training. In the supervised training phase, 5-fold cross-validation was used with 64 images for model training and 16 for validation, from one center. For testing, 20 hold-out images, evenly distributed between two centers, were used. Image segmentation and quantification metrics were evaluated on the test set compared to the ground-truth segmentation conducted by a nuclear medicine physician. RESULTS: The model generates high-quality OARs and lesion segmentation in lesion-positive cases, including mCRPC. The results show that self-supervised pre-training significantly improved the average dice similarity coefficient (DSC) for all classes by about 3%. Compared to nnU-Net, a well-established model in medical image segmentation, our approach outperformed with a 5% higher DSC. This improvement was attributed to our model's combined use of self-supervised pre-training and supervised fine-tuning, specifically when applied to PET/CT input. Our best model had the lowest DSC for lesions at 0.68 and the highest for liver at 0.95. CONCLUSIONS: We developed a state-of-the-art neural network using self-supervised pre-training on whole-body [68Ga]Ga-PSMA-11 PET/CT images, followed by fine-tuning on a limited set of annotated images. The model generates high-quality OARs and lesion segmentation for PSMA image analysis. The generalizable model holds potential for various clinical applications, including enhanced RLT and patient-specific internal dosimetry.

A dataset of [68Ga]Ga-Pentixafor PET/CT images of patients with high-grade Glioma.

This paper contains single-center prospective information showing illustrative examples of chemokine receptor-4 (CXCR4) targeting in high-grade glial brain tumors in treatment-naïve adult patients using a novel radiolabeled PET tracer: [68Ga]Ga-CXCR4 PET/CT. High-grade glioma is one of the most resistant malignancies to treatment. Despite major breakthroughs in diagnostic and therapeutic approaches, the overall 5-year survival rate remains in the 5-10% range. CXCR4 is a chemokine with the C-X-C motif that is overexpressed in high-grade gliomas. The 24 consecutive treatment- naïve enrolled patients underwent PET/CT images using the SIEMENS scanner (Biograph6 TrueV) and received the radiotracer intravenously. After approximately 60 min, the PET/CT acquisition was performed with a dedicated scanner and in 10 min time per bed position. The images were reconstructed and analyzed with the 3D-OSEM algorithm, applying point spread function (PSF) or resolution recovery algorithm (TrueX in Syngo ® software, Siemens Medical Solution), 3 iterations, and 21 subsets using a 3 mm Gaussian post-smoothing filter. These data would be potentially beneficial for automatic tumor delineation machine learning after augmented with other data retrieved from different papers as well as for differentiation between an active viable tumor vs. post-surgery/necrosis in indeterminate cases. The theranostics potential (CXCR4-tageted labeled beta emitters) is one of the most novel areas of interest for future studies.

Multicenter quantitative 18F-fluorodeoxyglucose positron emission tomography performance harmonization: use of hottest voxels towards more robust quantification.

Background: Harmonization methods reduce variability between different make and models of positron emission tomography (PET) scanners. The study aims to explore harmonization strategies that lead to comparable and robust quantitative metrics in a multicenter setting. Methods: NEMA IEC Phantom data acquisition was performed for low and high spheres-to-background ratios (SBR4:1 and 10:1) on six PET/CT (computed tomography) scanners. Different reconstruction sets, including the number of sub-iterations, number of subsets, and full width at half maximum (FWHM) for each scanner, were evaluated towards optimized and harmonized reconstruction settings. Recovery coefficients (RCs) of four quantitative metrics, including standardized uptake value (SUV)max, SUVISO-50 (SUVmean in 50% isocontour), SUVpeak, and mean uptake of 10 highest concentration voxels were evaluated as RCmax, RCISO-50, RCpeak, and RC10V, representing percent difference relative to the static ground truth case as functions of sphere sizes. A set of image reconstruction parameters was proposed for harmonized reconstruction to minimize variability between scanners. The root mean square error (RMSE), curvature, and reproducibility were examined. The proposed reconstruction protocols for harmonization and standard clinical reconstruction settings were compared to each other across all scanners. Results: A significant difference (P value <0.0001) was observed in the aforementioned quantitative metrics between SBR10 and SBR4. Reconstruction parameter sets with the smallest RMSE and RC values within 10% bias were identified as the best candidate for harmonization. The coefficient of variation of the mean value of RCs (CVMRC) shows a remarkable reduction of about 28%, 26%, 32%, and 19% in harmonized reconstruction settings for MRCmax, MRCISO-50, MRCpeak, and MRC10V, respectively. CVMRC for MRC10V in the harmonized reconstruction setting was 5.9% in SBR4, while the smallest value in SBR10 belongs to MRCpeak, with a value of 5.8%. The reproducibility of RC is improved by deriving the value from ten hottest voxels and is equally reproducible with RCpeak. Compared to RCmax and RCISO-50, the variability is reduced by 18% and 22% if ten voxels are pooled. Conclusions: Harmonizing PET/CT systems with and without point spread function/time of flight (PSF/TOF) using various vendor-developed image reconstruction algorithms improves the quantification reproducibility. RC10V, likewise RCpeak, is superior to the rest of the quantitative indices in terms of accuracy and reproducibility and helpful in quantifying lesion volume below 1 mL.

PET NEMA IQ Phantom dataset: image reconstruction settings for quantitative PET imaging.

The data presented here provide information about the role of reconstruction parameters on Positron Emission Tomography (PET) image quantification. Multiple phantom measurements in four different Spheres to Background Ratio (SBR) were performed on Biograph 6 TruePoint TrueV PET/CT scanner. PET raw data were reconstructed with/without resolution recovery algorithm using six various iteration x subsets with five different Full-Width Half-Maximum (FWHM) values of Gaussian post-smoothing filter. The Recovery Coefficient (RC) of six spheres using three common Volume of Interest (VOI) methods (max, 3D-50% Isocontour, and peak) were calculated. Moreover, SUVmax, SUVmean, and SUVpeak and volumetric indices, such as metabolic tumor volume (MTV), volume recovery coefficient (VRC), and total lesion glycolysis (TLG) were measured. RCmax, RC50%, and RCpeak as a function of sphere size were plotted in all reconstruction methods considering different SBRs. The data could be noticeable for standardization and optimization of quantitative metrics in PET imaging.

Regulation of XPA could play a role in inhibition of radiation-induced bystander effects in QU-DB cells at high doses.

INTRODUCTION: Radiation-induced bystander effects (RIBE) is the radiobiological effects detected in nonirradiated cells that have received signals from neighboring irradiated cells. In some studies, there are observations that RIBE unexpectedly reduces at high doses. In this study, the expression of two selected apoptotic and repair genes and their possible role in the formation of this unexpected reduction is examined. MATERIALS AND METHODS: The QU-DB cells were irradiated with gamma rays of a60 Co teletherapy unit at doses of 2, 4, 6, and 8 Gy. One hour following irradiation, their culture media were transferred to bystander cells to induced RIBE. After 24 h incubation, the RNA of cells was isolated and cDNA synthesized. Expression levels of BAX, XPA, and XPA/BAX ratio were examined by relative quantitative reverse transcription-polymerase chain reaction. RESULTS: In target cells, up-regulation of both genes was observed at all doses. In bystander cells, at the low dose (2 Gy), the expression of BAX was more than XPA; at 4 Gy, the ratio was balanced. A significant correlation was found between the XPA/BAX ratio and the dose, at high doses pattern of gene expression dominated by DNA repair gene. CONCLUSION: Gene expression profile was distinctive in bystander cells compared to target cells. The observed linear increasing of the ratio of XPA/BAX could support the hypothesis that the DNA repair system is stimulated and causes a reduction in RIBE at high doses.

PHA stimulation may be useful for FDXR gene expression-based biodosimetry.

OBJECTIVES: Nowadays, ionizing radiation (IR) has a significant contribution to the diagnostic and therapeutic medicine, and following that, health risks to individuals through unexpected exposure is greatly increased. Therefore, biological and molecular technology for estimation of dose (biodosimetry) is taken into consideration. In biodosimetry methods stimulation of cells to proliferation is routine to achieve more sensitivity of techniques. However, this concept has recently been challenged by new molecular methods such as gene expression analysis. This study aims to investigate the stimulation effects on gene expression biodosimetry. MATERIALS AND METHODS: The blood samples were taken from15 patients who were irradiated by TC-99 MIBI, before radiopharmaceutical injection and 24 hr after injection. Lymphocytes were extracted immediately and activated by (phytohemagglutinin) PHA for 24 hr and XPA and FDXR expression levels were investigated by employing relative quantitative Real-Time PCR. RESULTS: The results of this study show a significant increase in the FDXR expression level and a significant decrease in the XPA after stimulation of irradiated lymphocytes. Interestingly, a significant increasing trend in the FDXR expression level (at 0.05 significance level) following cell stimulation to the division was observed. CONCLUSION: Our results suggest that the PHA activation role in gene expression-based biodosimetry is strongly depended on the target genes and the relevant protein pathways. Finally, cell stimulation looks to be useful for some specific genes, such as FDXR, due to the increasing trend in expression and improvement of sensitivity of gene expression-based biodosimetry method.

In vivo Exposure Effects of 99mTc-methoxyisobutylisonitrile on the FDXR and XPA Genes Expression in Human Peripheral Blood Lymphocytes.

OBJECTIVES: In recent years, the application of radiopharmaceuticals in nuclear medicine has increased substantially. Following the diagnostic procedures performed in nuclear medicine departments, such as myocardial perfusion imaging, patients generally receive considerable doses of radiation. Normally, radiation-induced DNA damages are expected following exposure to a low-dose ionizing radiation. In order to detect molecular changes, high-sensitivity techniques must be utilized. The aim of this study was to assess the effect of a low-dose (below 10 mSv) gamma ray on gene expression using quantitative real-time polymerase chain reaction (qRT-PCR). METHODS: Blood samples were obtained from 20 volunteer patients who underwent myocardial perfusion imaging. They were given various doses of Technetium-99m methoxyisobutylisonitrile (99mTc-MIBI). After that, peripheral blood mononuclear cells (PBMNs) were derived, and then total RNA was extracted and reverse-transcribed to cDNA. Finally, the expression levels of xeroderma pigmentosum complementation group-A (XPA) and ferredoxin reductase (FDXR) genes were determinded through qRT-PCR technique using SYBR Green. RESULTS: XPA and FDXR expression levels were obtained following a very low-dose ionizing radiation. A significant up-regulation of both genes was observed, and the gene expression level of each individual patient was different. If differences in the administered activity and radiosensitivity are taken into account, the observed differences could be justified. Furthermore, gender and age did not play a significant role in the expression levels of the genes under study. CONCLUSION: The up-regulation of FDXR after irradiation revealed the high-sensitivity level of this gene; therefore, it could be used as an appropriate biomarker for biological dosimetry. On the other hand, the up-regulation of XPA is an indication of DNA repair following radiation exposure. According to linear no-threshold model (LNT) and the results obtained from this study, a very low dose of ionizing radiation could bring about adverse biological effects at molecular level in the irradiated person.