Radioimmunotherapy (RIT) in Brain Tumors

Annually, the incidence of brain tumors has slightly increased and also the patient prognosis is still disappointing, especially for high-grade neoplasms. So, researchers seek methods to improve therapeutic index as a critical aim of treatment. One of these new challenging methods is radioimmunotherapy (RIT) that involves recruiting a coupling of radionuclide component with monoclonal antibody (mAb) which are targeted against cell surface tumor–related antigens or antigens of cells within the tumor microenvironment. In the context of cancer care, precision medicine is exemplified by RIT; precision medicine can offer a tailored treatment to meet the needs for treatment of brain tumors. This review aims to discuss the molecular targets used in radioimmunotherapy of brain tumors, available and future radioimmunopharmaceutics, clinical trials of radioimmunotherapy in brain neoplasms, and eventually, conclusion and future perspective of application of radioimmunotherapy in neurooncology cancer care. © 2019, Korean Society of Nuclear Medicine

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

Objective(s): 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 sexmatched 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 ageand 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[removed]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. © 2021 mums.ac.ir All rights reserved

A cycle-consistent adversarial network for brain PET partial volume correction without prior anatomical information

Purpose: Partial volume effect (PVE) is a consequence of the limited spatial resolution of PET scanners. PVE can cause the intensity values of a particular voxel to be underestimated or overestimated due to the effect of surrounding tracer uptake. We propose a novel partial volume correction (PVC) technique to overcome the adverse effects of PVE on PET images. Methods: Two hundred and twelve clinical brain PET scans, including 50 18F-Fluorodeoxyglucose (18F-FDG), 50 18F-Flortaucipir, 36 18F-Flutemetamol, and 76 18F-FluoroDOPA, and their corresponding T1-weighted MR images were enrolled in this study. The Iterative Yang technique was used for PVC as a reference or surrogate of the ground truth for evaluation. A cycle-consistent adversarial network (CycleGAN) was trained to directly map non-PVC PET images to PVC PET images. Quantitative analysis using various metrics, including structural similarity index (SSIM), root mean squared error (RMSE), and peak signal-to-noise ratio (PSNR), was performed. Furthermore, voxel-wise and region-wise-based correlations of activity concentration between the predicted and reference images were evaluated through joint histogram and Bland and Altman analysis. In addition, radiomic analysis was performed by calculating 20 radiomic features within 83 brain regions. Finally, a voxel-wise two-sample t-test was used to compare the predicted PVC PET images with reference PVC images for each radiotracer. Results: The Bland and Altman analysis showed the largest and smallest variance for 18F-FDG (95% CI: − 0.29, + 0.33 SUV, mean = 0.02 SUV) and 18F-Flutemetamol (95% CI: − 0.26, + 0.24 SUV, mean = − 0.01 SUV), respectively. The PSNR was lowest (29.64 ± 1.13 dB) for 18F-FDG and highest (36.01 ± 3.26 dB) for 18F-Flutemetamol. The smallest and largest SSIM were achieved for 18F-FDG (0.93 ± 0.01) and 18F-Flutemetamol (0.97 ± 0.01), respectively. The average relative error for the kurtosis radiomic feature was 3.32%, 9.39%, 4.17%, and 4.55%, while it was 4.74%, 8.80%, 7.27%, and 6.81% for NGLDM_contrast feature for 18F-Flutemetamol, 18F-FluoroDOPA, 18F-FDG, and 18F-Flortaucipir, respectively. Conclusion: An end-to-end CycleGAN PVC method was developed and evaluated. Our model generates PVC images from the original non-PVC PET images without requiring additional anatomical information, such as MRI or CT. Our model eliminates the need for accurate registration or segmentation or PET scanner system response characterization. In addition, no assumptions regarding anatomical structure size, homogeneity, boundary, or background level are required. © 2023, The Author(s)

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. Voxelbased 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 [removed] 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

Feasibility and Therapeutic Potential of Peptide Receptor Radionuclide Therapy for High-Grade Gliomas

PURPOSE: This pilot study tested the principle that 177Lu-DOTATATE may be applied to patients with high-grade gliomas (HGGs) that are either inoperable or refractory to the standard conventional treatments and also assessed whether this approach could be a viable therapeutic plan in this dilemma. METHODS: In this prospective study, 16 subjects experiencing HGGs that were either inoperable or refractory to the standard conventional treatments were included. All the patients checked for somatostatin receptor expression on the tumors. The patients were treated with 1 to 4 cycles of IV 177Lu-DOTATATE. The primary end point was radiological response after peptide receptor radionuclide therapy, and the secondary end point was improved quality of life using Karnofsky Performance Score and Eastern Cooperative Oncology Group score. RESULTS: In total, 16 subjects (10 males and 6 females) with a mean age of 55.68 ± 13.17 years (26-73 years) participated in the study. Of them, 8 patients were new HGG cases, and 8 patients had recurrent tumors. The participants' responses to treatments were complete remission in 12.5% of (n = 2), partial remission in 31.25% (n = 5), disease stability in 18.7% (n = 3), and disease progression in 37.5% (n = 6). In total, pretreatment and posttreatment Karnofsky Performance Score and Eastern Cooperative Oncology Group scores did not improved (P > 0.05). The patients were followed up from 1 month to 26 months (median, 3 months). CONCLUSIONS: This preliminary result suggests that peptide receptor radionuclide therapy using 177Lu-DOTATATE may be associated with positive effects in patients with HGGs (grade III-IV). However, this approach should be evaluated in a more homogeneous group of patients with more favorable performance status

An update on PET-based molecular imaging in neuro-oncology: Challenges and implementation for a precision medicine approach in cancer care

PET imaging using novel radiotracers show promises for tumor grading and molecular characterization through visualizing molecular and functional properties of the tumors. Application of PET tracers in brain neoplasm depends on both type of the neoplasm and the research or clinical significance required to be addressed. In clinical neuro-oncology, 18F-FDG is used mainly to differentiate tumor recurrence from radiation-induced necrosis, and novel PET agents show attractive imaging properties. Novel PET tracers can offer biologic information not visible via contrast-enhanced MRI or 18F-FDG PET. This review aims to provide an update on the complementary role of PET imaging in neuro-oncology both in research and clinical settings along with presenting interesting cases in this context