Radiotracer Innovations in Breast Cancer Imaging: A Review of Recent Progress.

This review focuses on the pivotal role of radiotracers in breast cancer imaging, emphasizing their importance in accurate detection, staging, and treatment monitoring. Radiotracers, labeled with radioactive isotopes, are integral to various nuclear imaging techniques, including positron emission tomography (PET) and positron emission mammography (PEM). The most widely used radiotracer in breast cancer imaging is 18F-fluorodeoxyglucose (18F-FDG), which highlights areas of increased glucose metabolism, a hallmark of many cancer cells. This allows for the identification of primary tumors and metastatic sites and the assessment of tumor response to therapy. In addition to 18F-FDG, this review will explore newer radiotracers targeting specific receptors, such as estrogen receptors or HER2, which offer more personalized imaging options. These tracers provide valuable insights into the molecular characteristics of tumors, aiding in tailored treatment strategies. By integrating radiotracers into breast cancer management, clinicians can enhance early disease detection, monitor therapeutic efficacy, and guide interventions, ultimately improving patient outcomes. Ongoing research aimed at developing more specific and sensitive tracers will also be highlighted, underscoring their potential to advance precision medicine in breast cancer care.

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.

Initial clinical experience using 68Ga-FAPI-46 PET/CT for detecting various cancer types.

OBJECTIVE: Numerous studies have shown that gallium-68-labeled fibroblast activation protein inhibitor (68Ga-FAPI) positron emission tomography/computed tomography (PET/CT) scans would yield high intra-tumoral tracer uptake and low uptake in normal tissues as background, thus allowing for excellent visualization of lesions in the cancer microenvironment. This study set out to compare the suitability of novel 68Ga-FAPI-46 PET versus routine fluorine-18-fluorodeoxyglucose (18F-FDG) PET and other few cases of 68Ga-DOTATATE/68Ga-Pentixafor PET/CT for the assessment of different types of cancer. SUBJECTS AND METHODS: A retrospective analysis of 11 patients (6 males, 5 females; average age: 53 years, range: 10-58 years) with histopathologically confirmed, well-differentiated adenocarcinoma, medullar thyroid cancer (MTC), papillary thyroid carcinoma (PTC), cervical, gastric, glioblastoma multiform (GBM), colon, Ewing's sarcoma, and breast cancer was performed. These patients underwent PET/CT scans using four different radiotracers (9 18F-FDG, 11 68Ga- FAPI, 3 68Ga-DOTATATE, and 1 68Ga-Pentixafor). The patients' PET/CT images were visually evaluated for cancer detection, and analyzed semi-quantitatively through image- derived metrics, such as target-to-background ratio (TBR) and maximum standardized uptake value (SUVmax), for recurrence and metastasis. RESULTS: The study of 11 patients revealed that 68Ga-FAPI-46 was more effective than other tracers for detecting metastases, with 55 vs. 49 metastases in the lymph nodes, 4 vs. 3 in the liver, and 4 vs. 3 in the bones detected in comparison to 18F-FDG. No significant differences were observed in 68Ga-DOTATATE and 68Ga-Pentixafor PET images. In addition, in five patients, the SUVmax and TBR values in 68Ga-FAPI-46 PET images were significantly higher than those in 18F-FDG PET images for lymph nodes and bone metastases. Although the SUVmax in 68Ga-FAPI-46 and 18F-FDG PET images for liver metastases was comparable, 68Ga-FAPI- 46 had a significantly higher TBR than 18F-FDG. CONCLUSION: Our findings suggest that FAPI PET/CT is not suitable for evaluating GBM and Ewing sarcoma but generally outperforms 18F-FDG PET/CT in various types of breast cancer, gastrointestinal, gynecological, PTC and MTC. However, larger trials are needed to validate these preliminary findings.

An Update on the Role of mpMRI and 68Ga-PSMA PET Imaging in Primary and Recurrent Prostate Cancer.

The objective of this work was to review comparisons of the efficacy of 68Ga-PSMA-11 (prostate-specific membrane antigen) PET/CT and multiparametric magnetic resonance imaging (mpMRI) in the detection of prostate cancer among patients undergoing initial staging prior to radical prostatectomy or experiencing recurrent prostate cancer, based on histopathological data. A comprehensive search was conducted in PubMed and Web of Science, and relevant articles were analyzed with various parameters, including year of publication, study design, patient count, age, PSA (prostate-specific antigen) value, Gleason score, standardized uptake value (SUVmax), detection rate, treatment history, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and PI-RADS (prostate imaging reporting and data system) scores. Only studies directly comparing PSMA-PET and mpMRI were considered, while those examining combined accuracy or focusing on either modality alone were excluded. In total, 24 studies comprising 1717 patients were analyzed, with the most common indication for screening being staging, followed by relapse. The findings indicated that 68Ga-PSMA-PET/CT effectively diagnosed prostate cancer in patients with suspected or confirmed disease, and both methods exhibited comparable efficacy in identifying lesion-specific information. However, notable heterogeneity was observed, highlighting the necessity for standardization of imaging and histopathology systems to mitigate inter-study variability. Future research should prioritize evaluating the combined diagnostic performance of both modalities to enhance sensitivity and reduce unnecessary biopsies. Overall, the utilization of PSMA-PET and mpMRI in combination holds substantial potential for significantly advancing the diagnosis and management of prostate cancer.

Deep learning-based partial volume correction in standard and low-dose positron emission tomography-computed tomography imaging.

Background: Positron emission tomography (PET) imaging encounters the obstacle of partial volume effects, arising from its limited intrinsic resolution, giving rise to (I) considerable bias, particularly for structures comparable in size to the point spread function (PSF) of the system; and (II) blurred image edges and blending of textures along the borders. We set out to build a deep learning-based framework for predicting partial volume corrected full-dose (FD + PVC) images from either standard or low-dose (LD) PET images without requiring any anatomical data in order to provide a joint solution for partial volume correction and de-noise LD PET images. Methods: We trained a modified encoder-decoder U-Net network with standard of care or LD PET images as the input and FD + PVC images by six different PVC methods as the target. These six PVC approaches include geometric transfer matrix (GTM), multi-target correction (MTC), region-based voxel-wise correction (RBV), iterative Yang (IY), reblurred Van-Cittert (RVC), and Richardson-Lucy (RL). The proposed models were evaluated using standard criteria, such as peak signal-to-noise ratio (PSNR), root mean squared error (RMSE), structural similarity index (SSIM), relative bias, and absolute relative bias. Results: Different levels of error were observed for these partial volume correction methods, which were relatively smaller for GTM with a SSIM of 0.63 for LD and 0.29 for FD, IY with an SSIM of 0.63 for LD and 0.67 for FD, RBV with an SSIM of 0.57 for LD and 0.65 for FD, and RVC with an SSIM of 0.89 for LD and 0.94 for FD PVC approaches. However, large quantitative errors were observed for multi-target MTC with an RMSE of 2.71 for LD and 2.45 for FD and RL with an RMSE of 5 for LD and 3.27 for FD PVC approaches. Conclusions: We found that the proposed framework could effectively perform joint de-noising and partial volume correction for PET images with LD and FD input PET data (LD vs. FD). When no magnetic resonance imaging (MRI) images are available, the developed deep learning models could be used for partial volume correction on LD or standard PET-computed tomography (PET-CT) scans as an image quality enhancement technique.

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.

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.

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.

Remarkable FDG Uptake in Numerous Granulomatous Panniculitis Lesions: A Case Report.

ABSTRACT: A 42-year-old woman with history of rheumatoid arthritis and erythema nodosum from 8 years ago, who was treated with CellCept and prednisolone, was admitted to the rheumatology service due to skin lesions in the upper and lower extremities. Skin excisional biopsy was performed, and the results suggested panniculitis. FDG PET/CT was performed for malignancy workup. The scan images revealed intensely increased FDG uptake in all numerous subcutaneous nodules. FDG uptake in the panniculitis lesion is rarely reported in the literature.

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.

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.

Comparison of 18 F-NaF Imaging, 99m Tc-MDP Scintigraphy, and 18 F-FDG for Detecting Bone Metastases.

Bone is a common metastasis site in several malignancies, most importantly prostate and breast cancers. Given the significance of the early and accurate diagnosis of bone metastases for preliminary staging, treatment planning and monitoring, restaging, and survival prediction in patients with malignancy, it is critical to compare and contrast the strengths and weaknesses of imaging modalities. Although technetium-99m-labeled diphosphonates [ 99m Tc-MDP] scintigraphy has been used for assessing skeletal involvement, there is a renewed interest in fluorine-18-labeled sodium fluoride [ 18 F-NaF] bone imaging with positron emission tomography or positron emission tomography/computed tomography, since this approach provides essential advantages in bone metastases evaluation. This review study aimed to discuss the basic and technical aspects of 18 F-NaF imaging and its mechanism of action, and compare this modality with the 99m Tc-MDP bone scan and 18F-fluorodeoxyglucose using current evidence from the pertinent literature and case examples of the center in the study.

Multimodal assessment of regional gray matter integrity in early relapsing-remitting multiple sclerosis patients with normal cognition: a voxel-based structural and perfusion approach.

OBJECTIVE: There is increasing evidence that gray matter (GM) impairment is strongly associated with clinical performance decline. We aim to perform a voxelwise analysis between regional GM (rGM) perfusion and structural abnormalities in early relapsing-remitting multiple sclerosis patients with normal cognition (RRMS-IC) and explore clinical correlate of early rGM abnormalities. METHODS AND MATERIALS: We studied 14 early RRMS-IC patients and 14 healthy age- and sex-matched controls. Brain perfusion single photon emission computed tomography (SPECT), structural MRI, and a comprehensive neuropsychological examination were acquired from all participants. Neuropsychological tests include expanded disability status scale, minimal mental status examination, short physical performance battery, Wechsler memory scale, and quick smell test. Voxel-based morphometry was used for analyzing SPECT and T1-MR images to identify rGM hypoperfusion and atrophy, respectively (RRMS-IC vs controls (group analysis), and also, each patient vs controls (individual analysis)) (p < 0.001). Then, anatomical location of impaired regions was acquired by automated anatomical labeling software. RESULTS: There was no significant difference in total GM volume between RRMS-IC and healthy controls, however, rGM atrophy and hypoperfusion were detected. Individual analysis revealed more rGM impairment compared with group analysis. rGM hypoperfusion was more extensive rather than rGM atrophy in RRMS-IC. There was no spatial association between rGM atrophy and rGM hypoperfusion (p > 0.05). rGM abnormalities correlated with several relevant minimal clinical deficits. CONCLUSION: Lack of spatial correlation between rGM atrophy and hypoperfusion might suggest that independent mechanisms might underlie atrophy and hypoperfusion. Perfusion SPECT may provide supplementary information along with MRI. ADVANCES IN KNOWLEDGE: Association between rGM atrophy and rGM hypoperfusion and their clinical significance in early RRMS-IC is not well described yet. Our study showed that there is spatial dissociation between rGM atrophy and rGM hypoperfusion, suggesting that different mechanisms might underlie these pathologies.

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.

Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE in a Case of Concurrent Neuroendocrine Tumors and Meningioma: Achieving Two Things in a Single Action

We present a partial response of peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE in a case of concurrent neuroendocrine tumors (NETs) and meningioma. In addition to the valuable role of PRRT in inoperable NETs, it has been demonstrated that this treatment can be a promising therapy for progressive meningioma, especially in patients with low grade and refractory to standard regime.

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.

Feasibility of Deep Learning-Guided Attenuation and Scatter Correction of Whole-Body 68Ga-PSMA PET Studies in the Image Domain.

OBJECTIVE: This study evaluates the feasibility of direct scatter and attenuation correction of whole-body 68Ga-PSMA PET images in the image domain using deep learning. METHODS: Whole-body 68Ga-PSMA PET images of 399 subjects were used to train a residual deep learning model, taking PET non-attenuation-corrected images (PET-nonAC) as input and CT-based attenuation-corrected PET images (PET-CTAC) as target (reference). Forty-six whole-body 68Ga-PSMA PET images were used as an independent validation dataset. For validation, synthetic deep learning-based attenuation-corrected PET images were assessed considering the corresponding PET-CTAC images as reference. The evaluation metrics included the mean absolute error (MAE) of the SUV, peak signal-to-noise ratio, and structural similarity index (SSIM) in the whole body, as well as in different regions of the body, namely, head and neck, chest, and abdomen and pelvis. RESULTS: The deep learning-guided direct attenuation and scatter correction produced images of comparable visual quality to PET-CTAC images. It achieved an MAE, relative error (RE%), SSIM, and peak signal-to-noise ratio of 0.91 ± 0.29 (SUV), -2.46% ± 10.10%, 0.973 ± 0.034, and 48.171 ± 2.964, respectively, within whole-body images of the independent external validation dataset. The largest RE% was observed in the head and neck region (-5.62% ± 11.73%), although this region exhibited the highest value of SSIM metric (0.982 ± 0.024). The MAE (SUV) and RE% within the different regions of the body were less than 2.0% and 6%, respectively, indicating acceptable performance of the deep learning model. CONCLUSIONS: This work demonstrated the feasibility of direct attenuation and scatter correction of whole-body 68Ga-PSMA PET images in the image domain using deep learning with clinically tolerable errors. The technique has the potential of performing attenuation correction on stand-alone PET or PET/MRI systems.

Feasibility and Therapeutic Potential of Combined Peptide Receptor Radionuclide Therapy With Intensive Chemotherapy for Pediatric Patients With Relapsed or Refractory Metastatic Neuroblastoma.

BACKGROUND: Recent evidence has demonstrated high expression of somatostatin receptors in neuroblastoma (NB) cells. Because of this, we endeavored to evaluate the diagnostic performance and clinical efficacy of 68Ga-DOTATATE PET/CT and peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTATATE combined with chemotherapy in pediatric NB patients. PATIENTS AND METHODS: In total, 14 pediatric patients with histopathologically confirmed NB underwent 68Ga-DOTATATE PET/CT. Among them, the patients who were refractory or relapsed after therapy with 131I-MIBG and had intensive uptake of 68Ga-DOTATATE were referred for PRRT using 177Lu-DOTATATE. Treatment response based on follow-up imaging was classified into complete response, partial response, stable disease, and progressive disease. After each cycle of PRRT, laboratory tests were performed for evaluation of hematological, renal, and hepatic toxicities. The CTCAE (Common Terminology Criteria for Adverse Events; version 4.03) was used for grading adverse event. Curie score and International Society of Pediatric Oncology Europe Neuroblastoma score were used for semiquantitative analysis of scans of patients who underwent PRRT. In addition, overall survival was calculated as the time interval between the date of the first cycle and the end of follow-up or death. RESULTS: Overall, 14 refractory NB children including 7 boys and 7 girls with a median age of 5.5 years (ranged from 4 to 9) underwent 68Ga-DOTATATE PET/CT. PET/CT was positive in 10/14 patients (71.4%), and the median number of detected lesions in positive patients was 2 (range, 1-13). Of 14 patients, 5 patients underwent PRRT, including 3 boys and 2 girls. A total of 19 PRRT cycles and 66.4 GBq 177Lu-DOTATATE were given. Among these 5 patients, 2 showed an initial complete response, which relapsed a few months later, 1 showed a partial response, and 2 showed progressive disease. According to the Kaplan-Meier test, the overall survival was estimated at 14.5 months (95% confidence interval, 8.9-20.1). In evaluation of PRRT-related toxicity according to the CTCAE, 4 patients showed grade 1, and 1 showed grade 2 leukopenia. Two patients showed grade 1, and 2 others showed grade 2 anemia. Two patients showed grade 1, and 3 patients showed grade 2 thrombocytopenia. Serum creatinine in 1 patient increased to grade 1. CONCLUSIONS: Combination of 177Lu-DOTATATE with chemotherapeutic agents might achieve worthwhile responses with low toxicity, encouraging survival in NB patients who have relapsed or are refractory to conventional therapy, including 131I-MIBG therapy. Imaging with 68Ga-DOTATATE PET/CT in such patients has a relatively high detection efficacy, demonstrating its potential use as an alternative imaging tool to conventional modalities such as 123I/131I-MIBG. However, further well-designed trials are highly warranted.