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.

Radiomics and Artificial Intelligence in Radiotheranostics: A Review of Applications for Radioligands Targeting Somatostatin Receptors and Prostate-Specific Membrane Antigens.

Radiotheranostics refers to the pairing of radioactive imaging biomarkers with radioactive therapeutic compounds that deliver ionizing radiation. Given the introduction of very promising radiopharmaceuticals, the radiotheranostics approach is creating a novel paradigm in personalized, targeted radionuclide therapies (TRTs), also known as radiopharmaceuticals (RPTs). Radiotherapeutic pairs targeting somatostatin receptors (SSTR) and prostate-specific membrane antigens (PSMA) are increasingly being used to diagnose and treat patients with metastatic neuroendocrine tumors (NETs) and prostate cancer. In parallel, radiomics and artificial intelligence (AI), as important areas in quantitative image analysis, are paving the way for significantly enhanced workflows in diagnostic and theranostic fields, from data and image processing to clinical decision support, improving patient selection, personalized treatment strategies, response prediction, and prognostication. Furthermore, AI has the potential for tremendous effectiveness in patient dosimetry which copes with complex and time-consuming tasks in the RPT workflow. The present work provides a comprehensive overview of radiomics and AI application in radiotheranostics, focusing on pairs of SSTR- or PSMA-targeting radioligands, describing the fundamental concepts and specific imaging/treatment features. Our review includes ligands radiolabeled by 68Ga, 18F, 177Lu, 64Cu, 90Y, and 225Ac. Specifically, contributions via radiomics and AI towards improved image acquisition, reconstruction, treatment response, segmentation, restaging, lesion classification, dose prediction, and estimation as well as ongoing developments and future directions are discussed.

Pathogenic cis p-tau levels in CSF reflects severity of traumatic brain injury.

Traumatic brain injury (TBI) is the main cause of death and disability among young people. Following TBI, immune system activation and cytokine release induce kinase activity and hyperphosphorylation of tau protein, a structural molecule in axonal microtubules. The cis configuration of phosphorylated tau at Th231 is extremely neurotoxic and is having a prion nature, spreads to brain areas as well as CSF.We examined the cerebrospinal fluid (CSF) cis p-tau levels in 32 TBI patients and 5 non-TBI controls to find out the correlation with TBI severity.   CSF samples were drained 5-7 days after TBI and subjected for ELISA analysis with anti cis p-tau and ß-amyloid antibodies.We had no patients with mild TBI, two patients with moderate (6.2%), 23 patients with severe (71.9%), and 7 patients with critical TBI (21.9%). While mean CSF ß-amyloid in TBI and control groups did not show a statistically significant difference, the mean CSF cis p-tau level was significantly higher in the TBI group than the control samples. Also, intergroup analysis demonstrated that CSF cis p-tau levels were statistically different according to the head injury severity.Although CSF cis p-tau increased in the TBI patients, ß-amyloid did not show a significant difference between patients and controls. Also, we observed an obvious negative correlation between CSF cis p-tau levels and GCS scores. Therefore, future researches on suppression of cis P-tau production or removing previously produced cis P-tau could be a suitable approach in treating TBI in order to prevent tauopathies and future neurodegeneration.

A Prospective Study on [68Ga]-PSMA PET/CT Imaging in Newly Diagnosed Intermediate- and High-Risk Prostate Cancer.

OBJECTIVES: Prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography (PET/CT) is an emerging modality to detect metastatic disease in patients with prostate cancer (PCa). This prospective study aimed to evaluate the role of [68Ga]-PSMA PET/CT in the initial workup of intermediate and high-risk PCa. METHODS: Twenty-five patients with newly transrectal ultrasound biopsy-proven, untreated intermediate- and high-risk PCa (mean age, 68.5±6.2 years; range 55-83 years) were enrolled in this prospective study between September 2018 and June 2020 and underwent a [68Ga]-PSMA PET/CT examination. All images were analyzed both visually and semiquantitatively by measuring the maximum standardized uptake value (SUVmax) of the primary prostatic tumor and metastatic lesions. The diagnostic sensitivity of [68Ga]-PSMA PET/CT for the diagnosis of PCa was established by histopathology as the reference standard. The associations between SUVmax of the primary tumors and prostate-specific antigen (PSA) levels, Gleason scores (GSs), and metastatic extent of the disease were studied. RESULTS: All patients had a positive [68Ga]-PSMA PET/CT exam. Seventeen patients (58%) showed [68Ga]-PSMA avidity in both prostate lobes and 8 (32%) had unilateral uptake. SUVmax in the primary tumor significantly correlated with serum PSA values (r=0.57, P=0.003). PSMA PET/CT depicted regional lymph node metastases in 32% of patients, distant lymph node metastases in 20%, osseous metastases in 16% and pulmonary metastases in 8% of patients. Sixty percent of PSMA-positive bone metastases and 21.4% of intraprostatic tumoral lesions were missed on the contemporaneous bone scintigraphy and magnetic resonance imaging, respectively. CONCLUSION: [68Ga]-PSMA PET/CT shows promise as a valuable imaging modality with high diagnostic sensitivity in the setting of intermediate and high-risk PCa. Moreover, the SUVmax of the primary tumor has a positive correlation with PSA levels at the time of the scan.

2-[18F]FDG PET/CT radiomics in lung cancer: An overview of the technical aspect and its emerging role in management of the disease.

Lung cancer is the most common cancer, worldwide, and a major health issue with a remarkable mortality rate. 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) plays an indispensable role in the management of lung cancer patients. Long-established quantitative parameters such as size, density, and metabolic activity have been and are being employed in the current practice to enhance interpretation and improve diagnostic and prognostic value. The introduction of radiomics analysis revolutionized the quantitative evaluation of medical imaging, revealing data within images beyond visual interpretation. The "big data" are extracted from high-quality images and are converted into information that correlates to relevant genetic, pathologic, clinical, or prognostic features. Technically advanced, diverse methods have been implemented in different studies. The standardization of image acquisition, segmentation and features analysis is still a debated issue. Importantly, a body of features has been extracted and employed for diagnosis, staging, risk stratification, prognostication, and therapeutic response. 2-[18F]FDG PET/CT-derived features show promising value in non-invasively diagnosing the malignant nature of pulmonary nodules, differentiating lung cancer subtypes, and predicting response to different therapies as well as survival. In this review article, we aimed to provide an overview of the technical aspects used in radiomics analysis in non-small cell lung cancer (NSCLC) and elucidate the role of 2-[18F]FDG PET/CT-derived radiomics in the diagnosis, prognostication, and therapeutic response.

99mTc-PSMA SPECT/CT Versus 68Ga-PSMA PET/CT in the Evaluation of Metastatic Prostate Cancer.

BACKGROUND: 99mTc-prostate-specific membrane antigen (PSMA) SPECT/CT is less expensive and readily available modality compared with 68Ga-PSMA PET/CT for imaging prostate cancer (PC). The aim of this study is to compare the value of these 2 modalities in patients confirmed or suspicious to have metastatic prostate cancer. PATIENTS AND METHODS: Twenty-two patients with the mean age of 66.6 ± 10.1 years were studied using 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT, with less than 7 days interval between the 2 imaging procedures. Whole-body PET/CT was done 60 minutes after IV injection of 185 MBq (5 mCi) of 68Ga-PSMA. 99mTc-PSMA SPECT/CT was performed 3 hours after IV injection of 555 to 740 MBq (15-20 mCi) of 99mTc-PSMA. The images of each modality were interpreted independently, and the results were compared according to patient-based as well as region-based analyses. RESULTS: In patient-based evaluation, both 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT scans were positive in 95.45% (21/22). In region-based evaluation, 68Ga-PSMA PET/CT detected 53 regions (median of 2 regions per patient; range, 0-5), whereas 43 (median of 2 regions per patient; range, 0-5) were detected by 99mTc-PSMA SPECT/CT. Most of these differences could be explained by lower detection rate of 99mTc-PSMA SPECT/CT in prostate bed (n = 6). PET/CT detected more involved regions than SPECT/CT (P = 0.007), whereas similar frequency of extraprostatic lesions were diagnosed in both modalities (P = 0.102). Significant correlation was also demonstrated between serum prostate-specific antigen level and imaging parameters of disease extension detected by 2 modalities. CONCLUSIONS: 99mTc-PSMA SPECT/CT could be a potential substitute for 68Ga-PSMA PET/CT in high-risk patients, except when evaluation of prostate bed is of major concern.

68Ga-DOTATATE PET/CT Compared with 131I-MIBG SPECT/CT in the Evaluation of Neural Crest Tumors.

OBJECTIVES: 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) has shown promising results in imaging of neural crest tumors (NCT). Herein, we compared the performance of 68Ga-DOTATATE PET/CT and 131I-MIBG single photon emission computed tomography (SPECT)/CT in the initial diagnosis, staging and follow-up of patients with NCTs. METHODS: Twenty-five patients (males:females=8:17; age range=2-71 years) with clinically proven or suspicious neuroblastoma, pheochromocytoma (PCC) or paraganglioma (PGL) were enrolled in this prospective study and underwent both 68Ga-DOTATATE PET/CT and 131I-MIBG SPECT/CT. A composite reference standard derived from histopathological information, together with anatomical and functional imaging findings, was used to validate the results. Imaging findings were assessed on a per-patient and on a per-lesion basis. Sensitivity and accuracy were assessed using McNemar's test. RESULTS: Referring to radiological imaging and histopathological findings as reference standard, 68Ga-DOTATATE and 131I-MIBG scans showed a sensitivity and accuracy of (100%, 96%) and (86.7%, 88%), respectively, on a per-patient basis. In PCC/PGL patients, on a per-patient basis, the sensitivity of 68Ga-DOTATATE was 100% and that of 131I-MIBG was 77.8%. In neuroblastoma patients, on a per-patient basis, the sensitivities of both 68Ga-DOTATATE and 131I-MIBG were 100%. Overall, in this patient cohort, 68Ga-DOTATATE PET/CT identified 52 lesions and 131I-MIBG SPECT/CT identified only 30 lesions. On a per-lesion analysis, 68Ga-DOTATATE was found to be superior to 131I-MIBG in detecting lesions in all anatomical locations, particularly osseous lesions. According to the McNemar test results, differences were not statistically significant. CONCLUSION: This relatively small patient cohort suggests 68Ga-DOTATATE PET/CT be superior to 131I-MIBG SPECT/CT in providing particularly valuable information for both primary staging and follow-up in patients with NCT.

Molecular imaging of bone metastases using tumor-targeted tracers.

Bone metastasis is a disastrous manifestation of most malignancies, especially in breast, prostate and lung cancers. Since asymptomatic bone metastases are not uncommon, early detection, precise assessment, and localization of them are very important. Various imaging modalities have been employed in the setting of diagnosis of bone metastasis, from plain radiography and bone scintigraphy to SPECT, SPECT/CT, PET/CT, MRI. However, each modality showed its own limitation providing accurate diagnostic performance. In this regard, various tumor-targeted radiotracers have been introduced for molecular imaging of bone metastases using modern hybrid modalities. In this article we review the strength of different cancer-specific radiopharmaceuticals in the detection of bone metastases. As shown in the literature, among various tumor-targeted tracers, 68Ga DOTA-conjugated-peptides, 68Ga PSMA, 18F DOPA, 18F galacto-RGD integrin, 18F FDG, 11C/18F acetate, 11C/18F choline, 111In octreotide, 123/131I MIBG, 99mTc MIBI, and 201Tl have acceptable capabilities in detecting bone metastases depending on the cancer type. However, different study designs and gold standards among reviewed articles should be taken into consideration.

Risk Factors for Unfavorable Outcome in Aneurysmal Subarachnoid Hemorrhage Revisited; Odds and Ends.

OBJECTIVES: To evaluate the odds for unfavorable outcome of each risk factor and a combination of them in patients with aneurysmal subarachnoid hemorrhage (SAH) undergoing surgical clipping in Southern Iran. METHODS: A total of 367 patients who were operated between March 2007 and March 2016 due to aneurysmal SAH were analyzed according to patients' factors, aneurysm characteristics and intra-operative data. Correlation between outcomes of patients measured by modified Rankin Scale at 6-months with each factor were analyzed. Market Basket analysis was also used to identify the odds of unfavorable outcome for combinations of factors. RESULTS: A total of 367 patients, including 199 females and 168 males with a mean age of 47.27± 11.53 years, who underwent operation between March 2007 and March 2016 due to aneurysmal SAH were analyzed. Unlike gender, higher age was associated with unfavorable outcome. Ischemic heart disease, Duration of operation and amount of bleeding were also found to increase the odds of unfavorable outcome (p=0.01, 0.02, 0.04 respectively). DM, Cigarette smoking and opium addiction as well as the location and multiplicity of aneurysms did not have an adverse effect on outcome. (p≥0.05). CONCLUSION: Among the numerous risk factors presumed to result in unfavorable outcome in aneurysmal SAH, only older age, duration of operation more than 60 minutes, previous known history of ischemic heart disease, poorer clinical grade and intra-operative bleeding more than 500 mL were found to be significant factors.

Adherence to informed consent standards in Shiraz hospitals: matrons' perspective.

BACKGROUND: Informed consent is an important part of the patients' rights and hospitals are assigned to obtain informed consent before any diagnostic or therapeutic procedures. Obtaining an informed consent enables patients to accept or reject their care or treatments and prevent future contentions among patients and medical staff. METHODS: This survey was carried out during 2011-2. We assessed adherence of 33 Shiraz hospitals (governmental and non-governmental) to informed consent standards defined by Joint Commission International (JCI) Accreditation, USA. The questionnaire was designed using the Delphi method and then filled out by hospital matrons. We calculated valid percent frequency for each part of the questionnaire and compared these frequencies in governmental and non-governmental hospitals using analytical statistics. RESULTS: Considering 63% of the hospitals that filled out the questionnaire, no statistically significant difference was observed between the governmental and non-governmental hospitals in adherence to informed consent standards. CONCLUSION: This study shows a relatively acceptable adherence to standards about informed consent in Shiraz hospitals but the implementation seems not to be as satisfactory.