A convolutional neural network-based system for fully automatic segmentation of whole-body [68Ga]Ga-PSMA PET images in prostate cancer.

PURPOSE: The aim of this study was development and evaluation of a fully automated tool for the detection and segmentation of mPCa lesions in whole-body [68Ga]Ga-PSMA-11 PET scans by using a nnU-Net framework. METHODS: In this multicenter study, a cohort of 412 patients from three different center with all indication of PCa who underwent [68Ga]Ga-PSMA-11 PET/CT were enrolled. Two hundred cases of center 1 dataset were used for training the model. A fully 3D convolutional neural network (CNN) is proposed which is based on the self-configuring nnU-Net framework. A subset of center 1 dataset and cases of center 2 and center 3 were used for testing of model. The performance of the segmentation pipeline that was developed was evaluated by comparing the fully automatic segmentation mask with the manual segmentation of the corresponding internal and external test sets in three levels including patient-level scan classification, lesion-level detection, and voxel-level segmentation. In addition, for comparison of PET-derived quantitative biomarkers between automated and manual segmentation, whole-body PSMA tumor volume (PSMA-TV) and total lesions PSMA uptake (TL-PSMA) were calculated. RESULTS: In terms of patient-level classification, the model achieved an accuracy of 83%, sensitivity of 92%, PPV of 77%, and NPV of 91% for the internal testing set. For lesion-level detection, the model achieved an accuracy of 87-94%, sensitivity of 88-95%, PPV of 98-100%, and F1-score of 93-97% for all testing sets. For voxel-level segmentation, the automated method achieved average values of 65-70% for DSC, 72-79% for PPV, 53-58% for IoU, and 62-73% for sensitivity in all testing sets. In the evaluation of volumetric parameters, there was a strong correlation between the manual and automated measurements of PSMA-TV and TL-PSMA for all centers. CONCLUSIONS: The deep learning networks presented here offer promising solutions for automatically segmenting malignant lesions in prostate cancer patients using [68Ga]Ga-PSMA PET. These networks achieve a high level of accuracy in whole-body segmentation, as measured by the DSC and PPV at the voxel level. The resulting segmentations can be used for extraction of PET-derived quantitative biomarkers and utilized for treatment response assessment and radiomic studies.

Differential privacy preserved federated transfer learning for multi-institutional 68Ga-PET image artefact detection and disentanglement.

PURPOSE: Image artefacts continue to pose challenges in clinical molecular imaging, resulting in misdiagnoses, additional radiation doses to patients and financial costs. Mismatch and halo artefacts occur frequently in gallium-68 (68Ga)-labelled compounds whole-body PET/CT imaging. Correcting for these artefacts is not straightforward and requires algorithmic developments, given that conventional techniques have failed to address them adequately. In the current study, we employed differential privacy-preserving federated transfer learning (FTL) to manage clinical data sharing and tackle privacy issues for building centre-specific models that detect and correct artefacts present in PET images. METHODS: Altogether, 1413 patients with 68Ga prostate-specific membrane antigen (PSMA)/DOTA-TATE (TOC) PET/CT scans from 3 countries, including 8 different centres, were enrolled in this study. CT-based attenuation and scatter correction (CT-ASC) was used in all centres for quantitative PET reconstruction. Prior to model training, an experienced nuclear medicine physician reviewed all images to ensure the use of high-quality, artefact-free PET images (421 patients' images). A deep neural network (modified U2Net) was trained on 80% of the artefact-free PET images to utilize centre-based (CeBa), centralized (CeZe) and the proposed differential privacy FTL frameworks. Quantitative analysis was performed in 20% of the clean data (with no artefacts) in each centre. A panel of two nuclear medicine physicians conducted qualitative assessment of image quality, diagnostic confidence and image artefacts in 128 patients with artefacts (256 images for CT-ASC and FTL-ASC). RESULTS: The three approaches investigated in this study for 68Ga-PET imaging (CeBa, CeZe and FTL) resulted in a mean absolute error (MAE) of 0.42 ± 0.21 (CI 95%: 0.38 to 0.47), 0.32 ± 0.23 (CI 95%: 0.27 to 0.37) and 0.28 ± 0.15 (CI 95%: 0.25 to 0.31), respectively. Statistical analysis using the Wilcoxon test revealed significant differences between the three approaches, with FTL outperforming CeBa and CeZe (p-value < 0.05) in the clean test set. The qualitative assessment demonstrated that FTL-ASC significantly improved image quality and diagnostic confidence and decreased image artefacts, compared to CT-ASC in 68Ga-PET imaging. In addition, mismatch and halo artefacts were successfully detected and disentangled in the chest, abdomen and pelvic regions in 68Ga-PET imaging. CONCLUSION: The proposed approach benefits from using large datasets from multiple centres while preserving patient privacy. Qualitative assessment by nuclear medicine physicians showed that the proposed model correctly addressed two main challenging artefacts in 68Ga-PET imaging. This technique could be integrated in the clinic for 68Ga-PET imaging artefact detection and disentanglement using multicentric heterogeneous datasets.

The evaluation of protective and mitigating effects of vitamin C against side effects induced by radioiodine therapy.

The goal of this study was to evaluate the protective and mitigative effect of vitamin C on oxidative stress in differentiated thyroid cancer (DTC) patients ablated with radioiodine. 58 DTC patients selected for radioactive iodine therapy (RAIT) with 5550 MBq 131Iodine were divided into four groups. Group 1 (control group) consisted of patients who underwent RAIT routinely. Other patients received 1500 mg vitamin C daily 2 days after (group 2), 2 days before to 2 days after (group 3) and 2 days before RAIT (group 4). Serum oxidative stress markers including malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) were measured immediately before and 2 days after RAIT. A significant increase in MDA after RAIT was observed in all groups (p < 0.05). The concentrations of MDA were significantly higher in the control group compared to the intervention groups (p < 0.05). A significant decrease in the control group (p < 0.05) and increase in group 4 (p < 0.05) were observed in GSH level after RAIT (p < 0.05). Mean variation of GSH was significant between control group with groups 3 (p < 0.01) and 4 (p < 0.01). The results indicate that activity of SOD remained unchanged in all groups (p > 0.05). A significant increase was observed in CAT activity after RAIT in all groups (p < 0.05), which was higher in control group than intervention groups. In groups 3 (p < 0.05) and 4 (p < 0.05), this increase in CAT activity was significantly lower than the control group. RAIT causes serum oxidative stress, which can be ameliorated using vitamin C as an antioxidant. These results indicate that radioprotective effect of vitamin C is preferable to its mitigative effect.

Automated classification of Alzheimer's disease, mild cognitive impairment, and cognitively normal patients using 3D convolutional neural network and radiomic features from T1-weighted brain MRI: A comparative study on detection accuracy.

OBJECTIVES: Alzheimer's disease (AD) is a common neurodegenerative disorder that primarily affects older individuals. Due to its high incidence, an accurate and efficient stratification system could greatly aid in the clinical diagnosis and prognosis of AD patients. Convolutional neural networks (CNN) approaches have demonstrated exceptional performance in the automated stratification of AD, mild cognitive impairment (MCI) and cognitively normal (CN) participants using MRI, owing to their high predictive accuracy and reliability. Therefore, we aimed to develop an algorithm based on CNN and radiomic features derived from ROIs of bilateral hippocampus and amygdala in brain MRI for stratification between AD, MCI and CN. METHODS: In this study, we proposed a CNN and radiomic features-based algorithm using the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. T1-weighted images were used. We utilized three datasets, including AD (199 cases, 602 images), MCI (200 cases, 948 images), and CN (200 cases, 853 images), to perform binary classification (AD vs. CN, AD vs. MCI, and MCI vs. CN). Finally, we obtained the accuracy (ACC) and the area under the curve of the receiver operating characteristic curve (AUC) to evaluate the performance of the algorithm. RESULTS: Our proposed algorithm achieved acceptable overall discrimination accuracy. In the term of AD vs CN, radiomic-based algorithm alone obtained ACC of 82.6 % and AUC of 88.8, CNN-based algorithm obtained ACC of 80 % and AUC of 87.2 and their fusion showed ACC of 84.4 % and AUC of 90. In the term of MCI vs CN, radiomic-based algorithm alone obtained ACC of 71.6 % and AUC of 77.8, CNN-based algorithm obtained ACC of 69 % and AUC of 75 and their fusion showed ACC of 72.7 % and AUC of 80. In the term of AD vs MCI, radiomic-based algorithm alone obtained ACC of 57 % and AUC of 57.5, CNN-based algorithm obtained ACC of 56.6 % and AUC of 57.7 and their fusion showed ACC of 58 % and AUC of 59.5. CONCLUSION: In conclusion, it has been determined that hippocampus and amygdala-based stratification using CNN features and radiomic features-based algorithm is a promising method for the classification of AD, MCI, and CN participants. ADVANCES IN KNOWLEDGE: This study proposed an automated procedures based on MRI-derived radiomic features and CNN for classification between AD, MCI and CN.

Prognostic Significance of Baseline Clinical and [68Ga]Ga-PSMA PET Derived Parameters on Biochemical Response, Overall Survival, and PSA Progression-Free Survival in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Undergoing [177Lu]Lu-PSMA Therapy.

BACKGROUND: In this study, we sought to identify the clinical baseline characteristics and pre-therapy 68Ga-PSMA PET derived parameters that can have impact on PSA (biochemical) response, OS and PSA PFS in patients with metastatic castration-resistant prostate cancer (mCRPC) who undergo RLT with [177Lu]Lu-PSMA-617. METHODS: Various pre-treatment clinical and PSMA PET derived parameters were gathered and computed. We used PSA response as the criteria for more than a 50% decrease in PSA level, and OS and PSA PFS as endpoints. We assessed the collected parameters in relation to PSA response. Additionally, we employed univariable Cox regression and Kaplan-Meier analysis with log rank to evaluate the influence of the parameters on OS and PFS. RESULTS: A total of 125 mCRPC patients were included in this study. The median age was 68 years (range: 49-89). Among the cases, 77 patients (62%) showed PSARS, while 48 patients (38%) did not show PSA response. The median OS was 14 months (range: 1-60), and the median PSA-PFS was 10 months (range: 1-56). Age, prior history of chemotherapy, and SUVmax had a significant impact on PSA response (p<0.05). PSA response, RBC count, hemoglobin, hematocrit, neutrophil to lymphocyte ratio (NLR), alkaline phosphatase (ALP), number of metastases, wbPSMA-TV, and wbTL-PSMA significantly affected OS. GS, platelet count, NLR, and number of metastases were found to have a significant impact on PSA PFS. CONCLUSION: We have identified several baseline clinical and PSMA PET derived parameters that can serve as prognostic factors for predicting PSA response, OS, and PSA PFS after RLT. Based on the findings, we believe that these clinical baseline characteristics can assist nuclear medicine specialists in identifying RLT responders who have long-term survival and PFS.

Potential Role of Somatostatin Receptor Scintigraphy for In Vivo Imaging of Vulnerable Atherosclerotic Plaques and Its Association with Myocardial Perfusion Imaging Finding: A Preliminary Study.

Objectives: This study was conducted to detect atherosclerotic plaques with somatostatin receptor scintigraphy (SRS) using Tc-99m-octreotide that binds to somatostatin receptor-2. Methods: Of the 783 patients referred for myocardial perfusion imaging (MPI), 52 underwent additional chest single-photon emission computed tomography (SPECT) with Tc-99m-octreotide and participated in this study. In addition, 43 patients who underwent Tc-99m-octreotide scan for neuroendocrine tumor (NET) also received cardiac SPECT. Angiography was performed within 1 month after SRS for 19 patients who showed intensive uptake in SRS and had cardiac risk factors. Results: Of 52 patients who underwent MPI and SRS, 15 showed intensive cardiac uptake in SRS. Moreover, of 43 patients who were referred for NET, 4 patients had marked cardiac uptake in SRS in the heart. Nineteen patients including 12 women and 7 men aged 28 to 84 (58±8.04) years underwent coronary angiography. SRS and angiography in the left anterior descending territory were concordant in 15/19 (79%) patients, whereas only 7/15 (46%) cases had concordant MPI and angiography results. In the right coronary artery territory, SRS and angiography were concordant in 16/19 (84%) cases, while MPI and angiography were concordant in 11/15 (73%) cases. In the left circumflex artery territory, SRS and angiography were concordant in 15/19 (79%) cases, whereas MPI and angiography were concordant in 6/15 (40%) cases. In the remaining 76 patients who did not undergo coronary angiography based on cardiovascular profile and SRS, no cardiac events occurred in a follow-up of 2-11 months (7.52±2.71). Conclusion: Tc-99m-octreotide uptake was more concordant with coronary plaques relative to MPI findings, suggesting a potential role for Tc-99m-octreotide in the evaluation of atherosclerosis.

Initial Experience of 18 F-FET PET-MR Image Fusion for Evaluation of Recurrent Primary Brain Tumors.

Background An accurate monitoring technique is crucial in brain tumors to choose the best treatment approach after surgery and/or chemoradiation. Radiological assessment of brain tumors is widely based on the magnetic resonance imaging (MRI) modality in this regard; however, MRI criteria are unable to precisely differentiate tumoral tissue from treatment-related changes. This study was conducted to evaluate whether fused MRI and O-(2- 18 F-fluoroethyl)-L-tyrosine ( 18 F-FET) positron emission tomography (PET) can improve the diagnostic accuracy of the practitioners to discriminate treatment-related changes from true recurrence of brain tumor. Methods We retrospectively analyzed 18 F-FET PET/computed tomography (CT) of 11 patients with histopathologically proven brain tumors that were suspicious for recurrence changes after 3 to 4 months of surgery. All the patients underwent MRI and 18 F-FET PET/CT. As a third assessment, fused 18 F-FET PET/MRI was also acquired. Finally, the diagnostic accuracy of the applied modalities was compared. Results Eleven patients aged 27 to 73 years with a mean age of 47 ± 13 years were enrolled. According to the results, 9/11 cases (82%) showed positive MRI and 6 cases (55%) showed positive PET/CT and PET/MRI. Tumoral recurrence was observed in six patients (55%) in the follow-up period. Based on the follow-up results, accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 64, 85, 25, 67, and 50%, respectively, for MRI alone and 91, 85, 100, 100, and 80%, respectively, for both PET/CT and PET/MRI. Conclusion This study found that 18 F-FET PET-MR image fusion in the management of brain tumors might improve recurrence detection; however, further well-designed studies are needed to verify these preliminary data.

Feasibility and therapeutic potential of the 68Ga/177Lu-DOTATATE theranostic pair in patients with metastatic medullary thyroid carcinoma.

BACKGROUND: This study assessed: 1) the clinical efficacy of imaging with 68Ga-DOTATATE PET/CT (SSTR (somatostatin receptor)-PET) to detect medullary thyroid carcinoma (MTC); and 2) the therapeutic efficacy of peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE in MTC patients. MATERIALS AND METHODS: Patients with histologically proven MTC and suspected recurrence following thyroidectomy, based on raised serum calcitonin levels, underwent SSTR-PET. In addition, to evaluate the clinical efficacy and safety of PRRT, the patients with intense uptake on SSTR-PET or 99mTc-octreotide scintigraphy underwent PRRT. The Common Terminology Criteria for Adverse Events (version 4.03) was used to grade adverse events after PRRT. Treatment response was classified as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). RESULTS: Twenty MTC patients (10 male, 10 female) with a median age of 48.5 years underwent SSTR-PET. SSTR-PET was positive in 17/20 patients (85%). Four of the 17 patients with positive SSTR-PET were scheduled for PRRT. In addition, 2 patients had positive 99mTc-octreotide scintigraphy results (Krenning score ≥ 2) and were scheduled for PRRT. Two of the 6 patients who underwent PRRT showed PR, 2 SD and 2 PD. Two patients died during the follow-up period. Median overall survival was 19 months (95% CI: 5.52-29.48). There were no cases of significant toxicity. CONCLUSION: Radiolabeled somatostatin analogs are contributive for the management of recurrent MTC. 68Ga-DOTATAE PET-CT showed a relatively high detection rate in recurrent MTC. In addition, PRRT with 177Lu-DOTATATE was found to be a safe alternative therapeutic option for MTC.

Artificial intelligence-based analysis of whole-body bone scintigraphy: The quest for the optimal deep learning algorithm and comparison with human observer performance.

PURPOSE: Whole-body bone scintigraphy (WBS) is one of the most widely used modalities in diagnosing malignant bone diseases during the early stages. However, the procedure is time-consuming and requires vigour and experience. Moreover, interpretation of WBS scans in the early stages of the disorders might be challenging because the patterns often reflect normal appearance that is prone to subjective interpretation. To simplify the gruelling, subjective, and prone-to-error task of interpreting WBS scans, we developed deep learning (DL) models to automate two major analyses, namely (i) classification of scans into normal and abnormal and (ii) discrimination between malignant and non-neoplastic bone diseases, and compared their performance with human observers. MATERIALS AND METHODS: After applying our exclusion criteria on 7188 patients from three different centers, 3772 and 2248 patients were enrolled for the first and second analyses, respectively. Data were split into two parts, including training and testing, while a fraction of training data were considered for validation. Ten different CNN models were applied to single- and dual-view input (posterior and anterior views) modes to find the optimal model for each analysis. In addition, three different methods, including squeeze-and-excitation (SE), spatial pyramid pooling (SPP), and attention-augmented (AA), were used to aggregate the features for dual-view input models. Model performance was reported through area under the receiver operating characteristic (ROC) curve (AUC), accuracy, sensitivity, and specificity and was compared with the DeLong test applied to ROC curves. The test dataset was evaluated by three nuclear medicine physicians (NMPs) with different levels of experience to compare the performance of AI and human observers. RESULTS: DenseNet121_AA (DensNet121, with dual-view input aggregated by AA) and InceptionResNetV2_SPP achieved the highest performance (AUC = 0.72) for the first and second analyses, respectively. Moreover, on average, in the first analysis, Inception V3 and InceptionResNetV2 CNN models and dual-view input with AA aggregating method had superior performance. In addition, in the second analysis, DenseNet121 and InceptionResNetV2 as CNN methods and dual-view input with AA aggregating method achieved the best results. Conversely, the performance of AI models was significantly higher than human observers for the first analysis, whereas their performance was comparable in the second analysis, although the AI model assessed the scans in a drastically lower time. CONCLUSION: Using the models designed in this study, a positive step can be taken toward improving and optimizing WBS interpretation. By training DL models with larger and more diverse cohorts, AI could potentially be used to assist physicians in the assessment of WBS images.

Predictive and prognostic potential of pretreatment 68Ga-PSMA PET tumor heterogeneity index in patients with metastatic castration-resistant prostate cancer treated with 177Lu-PSMA.

Introduction: This study was conducted to evaluate the predictive values of volumetric parameters and radiomic features (RFs) extracted from pretreatment 68Ga-PSMA PET and baseline clinical parameters in response to 177Lu-PSMA therapy. Materials and methods: In this retrospective multicenter study, mCRPC patients undergoing 177Lu-PSMA therapy were enrolled. According to the outcome of therapy, the patients were classified into two groups including positive biochemical response (BCR) (≥ 50% reduction in the serum PSA value) and negative BCR (< 50%). Sixty-five RFs, eight volumetric parameters, and also seventeen clinical parameters were evaluated for the prediction of BCR. In addition, the impact of such parameters on overall survival (OS) was evaluated. Results: 33 prostate cancer patients with a median age of 69 years (range: 49-89) were enrolled. BCR was observed in 22 cases (66%), and 16 cases (48.5%) died during the follow-up time. The results of Spearman correlation test indicated a significant relationship between BCR and treatment cycle, administered dose, HISTO energy, GLCM entropy, and GLZLM LZLGE (p<0.05). In addition, according to the Mann-Whitney U test, age, cycle, dose, GLCM entropy, and GLZLM LZLGE were significantly different between BCR and non BCR patients (p<0.05). According to the ROC curve analysis for feature selection for prediction of BCR, GLCM entropy, age, treatment cycle, and administered dose showed acceptable results (p<0.05). According to SVM for assessing the best model for prediction of response to therapy, GLCM entropy alone showed the highest predictive performance in treatment planning. For the entire cohort, the Kaplan-Meier test revealed a median OS of 21 months (95% CI: 12.12-29.88). The median OS was estimated at 26 months (95% CI: 17.43-34.56) for BCR patients and 13 months (95% CI: 9.18-16.81) for non BCR patients. Among all variables included in the Kaplan Meier, the only response to therapy was statistically significant (p=0.01). Conclusion: This exploratory study showed that the heterogeneity parameter of pretreatment 68Ga-PSMA PET images might be a potential predictive value for response to 177Lu-PSMA therapy in mCRPC; however, further prospective studies need to be carried out to verify these findings.

Peptide Receptor Radionuclide Therapy Using 177 Lu-DOTATATE in Advanced Neuroendocrine Tumors (NETs) in a Limited-Resource Environment.

Background This study was conducted to evaluate the clinical efficacy and safety of peptide receptor radionuclide therapy (PRRT) using 177 Lu-DOTA0-Tyr3-octreotate (DOTATATE) in patients with neuroendocrine tumors (NETs). Methods Sixteen patients with pathologically verified NETs including eight females and eight males were enrolled in this study. Before PRRT, the patients underwent 68 Ga-DOTATATE positron emission tomography/computed tomography or 99m Tc-octreotide scintigraphy for evaluation of somatostatin receptor expression. Response to treatment was assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) classified as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). In addition, for evaluation of toxicity, monthly blood analysis was performed including hematology, renal function (creatinine) test, and liver function test. The Eastern Cooperative Oncology Group (ECOG) status performance was applied to estimate the patients' general condition in a scale of 0 (fully active) to 5 (dead). In addition, overall survival (OS) was calculated as the time interval from the start of PRRT to death from any reason. Results Sixteen patients including eight females and eight males with a median age of 60.5 years (range: 24-74) were enrolled in this study. The patients underwent PRRT with a median cycle of 3.5 (range: 1-7) and a median dose of 20.35 (range: 7.4-49.95 GBq). At the end of data collection, PR, CR, SD, and PD were seen in 11, 2, 1, and 2 patients according to the RECIST, respectively. Three patients expired during or after the PRRT period. The median ECOG and Karnofsky Performance Scale was 1.5 and 75 before PRRT, which improved significantly to 1 and 80 after PRRT, respectively ( p < 0.05). According to the Kaplan-Meier test, the median OS was 23 months (95% confidence interval: 7.90-38.09). According to the National Cancer Institute's Common Terminology Criteria for Adverse Events, three patients showed grade I and three patients showed grade II leucopenia. Furthermore, three and seven patients had grade II and grade I anemia, respectively. Conclusion Since PRRT using 177 Lu-DOTATATE has a favorable response rate and few adverse effects and improves the quality of life in NETs, it can be used as an effective therapeutic option, especially in nonoperative, metastatic, and progressive NETs.

Cardiotoxicity and cardiac monitoring following the use of radiotheranostics agents including 177Lu-PSMA for prostate cancer and 177Lu-DOTATATE for neuroendocrine tumors.

BACKGROUND: The aim of this study was to determine the probable cardiotoxicity following radionuclide therapy (RNT), specifically peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE and radioligand therapy (RLT) with 177Lu-PSMA by evaluation of serum troponin I and cardiac profile change during a follow-up time. MATERIALS AND METHODS: Patients with prostate cancer and neuroendocrine tumours (NETs) referred for PRRT and RLT, respectively, were enrolled in this study. The cardiac profiles of the patients were evaluated by a cardiologist and a cardiac history was obtained from all patients. Also, troponin I was measured before and 48 hours after treatment. RESULTS: In this retrospective study for assessment of RLT associated cardiotoxicity, 24 patients were evaluated with a median age of 64 years (27-99 years) including 13 NET patients and 11 prostate cancer patients. Patients were followed up for 4 to 31 months which no cardiovascular problem was observed. In evaluation of troponin I, 39 RNT cycles were evaluated. In all patients, the value of troponin I was in normal range. In all patients, the median values of serum troponin I before and after treatment were 0.2 ±â€Š0.02 (range: 0.00-0.42) and 0.28 ±â€Š0.02 (range: 0.00-0.46) ng/ml, respectively (p > 0.05). In the prostate cancer patients, the median values of serum troponin I before and after treatment were 0.26 ± 0.04 (0.04-0.42) and 0.30 ±â€Š0.04 (0.00-0.41) ng/ml, respectively (p > 0.05). In the NET patients, the median values of serum troponin I before and after treatment were 0.18 ± 0.03 (0.00-0.42) and 0.17 ±â€Š0.03 (0.00-0.46) ng/ml, respectively (p > 0.05). CONCLUSION: PRRT with 177Lu-DOTATATE and RLT with 177Lu-PSMA as emerging therapeutic modalities have no significant cardiotoxicity. However, further well-designed studies are recommended.

Somatostatin Receptor Scintigraphy in a Patient with Myocarditis

We report a case of myocarditis imaged with technetium-99m octreotide cardiac single-photon emission computed tomography which showed diffuse uptake in the myocardium, indicating inflammatory reaction to myocardial damage. Somatostatin receptor scintigraphy of the heart could be considered in patients with suspected cardiac inflammation. This could facilitate early diagnosis and guide appropriate treatment.

Assessment of early oxidative stress following the use of radiotheranostics agents 177Lu-PSMA for prostate cancer and 177Lu-DOTATATE for neuroendocrine tumors; radioprotective effect of vitamin C.

BACKGROUND: We aimed first to evaluate the early oxidative stress following radionuclide therapy (RNT) with 177Lu-PSMA and 177Lu-DOTATATE and second to evaluate the protective effect of vitamin C on oxidative stress. MATERIALS AND METHODS: Prostate cancer and neuroendocrine tumor (NET) patients referred to therapy with 177Lu-PSMA and 177Lu-DOTATATE, respectively, were enrolled in this study. The patients divided into the control group underwent routine RNT without any intervention and the intervention group was asked to take effervescent tablets (500 mg) of vitamin C for two days prior to the RNT (three tablets per day). To measure oxidative stress, blood samples were taken immediately before treatment and 48 h after treatment, and the serums were separated and frozen. To evaluate oxidative stress, the serum levels of malondialdehyde (MDA) and glutathione (GSH) and the activity of glutathione reductase were measured before and two days after treatment. RESULTS: In total, 61 RNT cycles were evaluated in 34 patients with age of 65 ± 2.83 (median ± SE) years (range of 27-99); this total included 20 (59%) prostate cancer patients [35 cycles (57.4%)] and 14 patients (41%) with NET [26 cycles (42.6%)]. Of the 61 evaluated cycles, 27 cycles were given in the control group and 34 cycles were given in the intervention group. The serum level of MDA was significantly increased after treatment compared to before treatment (P = 0.02) in the control group, while no significant change in the serum level of MDA was observed in the intervention group (P = 0.52). The serum level of GSH was insignificantly decreased after treatment compared to before treatment in the control group and slightly increased after treatment in the intervention group (P > 0.05). The serum level of glutathione reductase was insignificantly increased in all groups of patients after treatment (P > 0.05). CONCLUSION: According to the results of this study, RNT with Lu-PSMA and Lu-DOTATATE may induce oxidative stress via the generation of free radicals and reactive oxygen species. Consumption of vitamin C prior to RNT may ameliorate this oxidative stress. These preliminary results have positive implications for clinical practice. Verification of these noteworthy results is needed and can be conducted with larger randomized controlled trials with longer time points.

Evaluation of myocardial perfusion and function in patients with asymptomatic beta-thalassemia major using myocardial gated single-photon-emission computed tomography.

This study was conducted to evaluate the cardiac perfusion and function of patients with beta-thalassemia major (TM) using99mTc-MIBI cardiac gated single-photon-emission computed tomography (SPECT) and to compare the obtained indices with echocardiographic and hematological parameters. Patients with TM who were referred for regular blood transfusion and periodic checkup were included in this study. A questionnaire containing demographic and medical data was provided for all patients by an expert pediatrician. All of the patients were on Desferal chelation therapy and none of them had clinical signs of heart failure. Myocardial gated perfusion SPECT, echocardiography, and complete blood tests were performed for each patient. In total, 24 patients including 14 men (58.3%) and 10 women (41.7%) aged 15-36 years with a mean age of 24.3 ± 6.5 years' old were enrolled in this study. Myocardial perfusion scan (MPS) was normal in all patients. The mean value of the measured left ventricular ejection fraction (LVEF) was 58.88 ± 13.45%. There was no significant association between measured LVEF on scan and echocardiography (P > 0.05). In terms of hematological results, there was a significant association between the hemoglobin and ferritin level and the amount of blood transfusion (P = 0.02 and P= 0.00, respectively). According to the results of myocardial perfusion imaging (MPI), cardiac perfusion and LVEF were within normal limits in all asymptomatic patients. In the absence of any perfusion abnormality, the use of MPI in patients with asymptomatic beta-TM is not recommended for diagnosing myocardial ischemia.

Dual-phase 68Ga-PSMA-11 PET/CT may increase the rate of detected lesions in prostate cancer patients.

BACKGROUND: This study was conducted to compare the early static (3-6 min post-injection (p.i.)) and standard whole body (1 h, p.i.) 68Ga-PSMA-11 PET/CT imaging for detection of lesions in prostate cancer (PC) patients. MATERIALS AND METHODS: In this study, PC patients suspected of recurrence underwent 68Ga-PSMA-11 PET/CT. Early static images were acquired from the pelvis and the lower abdomen 3-5 minutes after radiotracer injection and, a routine whole body scan was performed from the skull to the mid-thigh 1 h after injection. Quantitative analysis (SUVmax) was evaluated in suspicious lesions. RESULTS: Of 19 evaluated PC patients with a median age of 72 ± 1.66 years (range: 55-85 years) and prostate-specific antigen (PSA) of 1.72 ± 6.11 ng/ml (range: 0.1-100 ng/ml) (median ± SE), 16 showed positive in the whole body PET/CT. All of the patients with positive whole body scans due to pelvic involvement had positive early scan results. Totally, 22 lesions were detected in both early and delay scans in the pelvic which 16 were related to prostate involvement, 4 were related to lymph node involvement, and 2 were related to bone involvement. Moreover, in addition to the mentioned 22 lesions, early PET imaging successfully detected local recurrence in a patient who was negative on WB PET/ CT; this lesion was masked in the delay scan due to bladder activity. The median SUVmax values of the early and delay scans were 3.69 ± 1.07 (median ± SE) (range: 1.2-14.5) and 5.85 ± 1.69 (range: 3.1-23.4), respectively. (p = 0.005). CONCLUSION: Early static 68Ga-PSMA-11 PET/CT imaging might discriminate metastases from urinary bladder activity. Therefore, early static imaging in combination with whole body 60-min p.i. imaging can improve the detection of local involvement pelvic disease.

Theranostics in Brain Tumors.

Theranostic nuclear oncology, mainly in neuro-oncology (neurotheranostics), aims to combine cancer imaging and therapy using the same targeting molecule. This approach tries to identify patients who are most likely to benefit from tumor molecular radionuclide therapy. The ability of radioneurotheranostic agents to interact with cancer cells at the molecular level with high specificity can significantly improve the effectiveness of cancer therapy. A variety of biologic targets are under investigation for treating brain tumors. PET-based precision imaging can substantially improve the therapeutic efficacy of radiotheranostic approach in brain tumors.

Association of regional cerebral perfusion impairment with gait and balance performance in dizzy patients using brain perfusion SPECT: Voxel-based analysis of a pilot sample.

OBJECTIVES: The purpose of this study was to investigate regional cerebral blood flow (rCBF) reduction in patients with dizziness and perfusion-related clinical impairment using brain perfusion single photon emission tomography (SPECT). METHODS: Thirty-four patients with subjective dizziness and 13 age- and sex-matched healthy controls were studied. Dizziness-related impairments were assessed using the Dizziness Handicap Inventory (DHI) and Short Physical Performance Battery (SPPB). Brain perfusion SPECT scan was acquired from all participants. The carotid intima-media thickness (CIMT) was also measured. Brain perfusion data were qualitatively interpreted in all cases. Voxel-wise analysis was also conducted in 11 patients compared to healthy controls. RESULTS: Thirty-four patients (mean age=53.8±13.4 years, m/f: 19/15) and 13 age- and sex-matched controls (mean age=51.5±13.1, m/f: 7/6) were included. The dizziness severity was mild in 58.8% (n=20), moderate in 26.5% (n=9), and severe in 14.7% (n=5). Qualitative interpretation of SPECT images showed normal scans in 4 (11.2%) patients and abnormal scans in 30 (88.2%) patients. Patients with dizziness showed a significantly decreased brain perfusion in the precuneus, cuneus, occipital lobe (superior and inferior parts), frontal lobe (inferior and middle parts), temporal lobe, parietal lobe (inferior and superior parts), cerebellum, insula, and putamen nucleus. Based on both qualitative SPECT interpretation and voxel-wise analysis, perfusion defect had a significant association with the total SPPB score and the scores of two sub-domains (p<0.05), but not with the DHI (p>0.05) score. CONCLUSION: The perfusion- and atherosclerosis-related impairments of gait and balance were largely independent of subjective dizziness and dizziness severity. Moreover, this study provided support for contribution of perfusion impairment to the disturbance of gait and balance in older populations along with other pathologic processes.

Theranostic Approach in Breast Cancer: A Treasured Tailor for Future Oncology.

ABSTRACT: Breast cancer is the most frequent invasive malignancy and the second major cause of cancer death in female subjects mostly due to the considerable diagnostic delay and failure of therapeutic strategies. Thus, early diagnosis and possibility to monitor response to the treatment are of utmost importance. Identification of valid biomarkers, in particular new molecular therapeutic targets, that would allow screening, early patient identification, prediction of disease aggressiveness, and monitoring response to the therapeutic regimen has been in the focus of breast cancer research during recent decades. One of the intensively developing fields is nuclear medicine combining molecular diagnostic imaging and subsequent (radio)therapy in the light of theranostics. This review aimed to survey the current status of preclinical and clinical research using theranostic approach in breast cancer patients with potential to translate into conventional treatment strategies alone or in combination with other common treatments, especially in aggressive and resistant types of breast cancer. In addition, we present 5 patients with breast cancer who were refractory or relapsed after conventional therapy while presumably responded to the molecular radiotherapy with 177Lu-trastuzumab (Herceptin), 177Lu-DOTATATE, and 177Lu-FAPI-46.