[18F]FDOPA PET/CT in Solid Pseudopapillary Tumor of the Pancreas: a Recurred Tumor Mimicking Splenosis.

Solid pseudopapillary tumor (SPT) of the pancreas is a neoplasm with low malignant potential. It is often challenging to diagnose SPT due to its nonspecific clinical and radiological features, and [18F]FDOPA is effective in diagnosing SPT, particularly in differentiating SPT from benign conditions such as splenosis. A 55-year-old woman underwent distal pancreatectomy and splenectomy for histologically confirmed SPT. She was also initially diagnosed with splenosis. During follow-up, sizes of multiple nodular lesions were increased, raising the possibility of peritoneal seeding of SPT. For diagnosis, a spleen scan and SPECT/CT were performed using 99mTc-labeled damaged red blood cells, which showed no uptake in the peritoneal nodules. Subsequent [18F]FDOPA PET/CT revealed [18F]FDOPA-avidity of the nodules. The patient underwent tumor resection surgery, and the nodules were pathologically confirmed as SPT.

Simplified image-based dosimetry using planar images and patient-specific S-values.

BACKGROUND: Single time point measurement approach and hybrid dosimetry were proposed to simplify the dosimetry process. It is anticipated that utilizing patient-specific S-value would enable more accurate dosimetry assessment based on imaging compared to using the conventional MIRD S-values. PURPOSE: We performed planar image-based dosimetry scaled with a single SPECT image for the entire treatment cycle using patient-specific S-values (PSS dosimetry) of organs. PSS dosimetry could further simplify the dosimetry procedure compared with a conventional 2D planar/3D SPECT hybrid dosimetry, as PSS dosimetry requires only one SPECT/CT image for the treatment of the entire cycle, whereas the conventional hybrid dosimetry requires a SPECT/CT image for each treatment cycle. METHODS: 177Lu-DOTATATE SPECT/CT and planar image datasets acquired from Seoul National University Hospital (SNUH, Seoul, Republic of Korea) were utilized for the evaluation. Images were acquired 4, 24, 48, and 120 h after patients' intravenous injection of 177Lu-DOTATATE. Dose estimations based on a Monte Carlo (MC) simulation using the Geant4 Application for Emission Tomography (GATE) (v.8.2) were considered as the reference. Planar image-based dosimetry scaled with a single SPECT image was performed using the patient-specific S-value (PSS). Briefly, the CT image was considered as the patient's anatomical reference and PSSs were quantified using the multiple voxel S-value (VSV) method. Then, PSS dosimetry was performed by obtaining activity information from sequential planar images and a scaling factor derived from a single SPECT/planar image pair. Hybrid dosimetry using sequential planar images and a single SPECT image was performed for comparison. The absorbed doses of the kidneys, bone marrow (BM) in the lumbar spine, liver, and spleen calculated using the PSS and hybrid dosimetries were compared with the reference MC results. RESULTS: The mean differences (MDs) of the self-absorption S-values between S-value of OLINDA/EXM and PSS for the kidneys, liver, and spleen were -0.04%, -2.39%, and -2.62%, respectively. However, the differences in the self-absorption S-values were significantly higher for the BM (84.99%) and the remainder of the body (ROB) (280.84%). The absorbed doses estimated by the PSS and hybrid dosimetries showed relatively high errors compared with MC simulation result, regardless of the organ. In contrast, the PSS and hybrid dosimetries produced similar dose estimates. For the entire cycles of the treatment, the MDs of absorbed doses between PSS and hybrid dosimetries were -3.31%, -6.04%, 3.37%, and -2.17% for the kidneys, BM, liver, and spleen, respectively. Through a correlation analysis and the Wilcoxon signed-rank test, we concluded that there was no significant difference between the results obtained by the two dosimetry methods. CONCLUSIONS: As the PSS was derived using CT images with actual anatomical information and organ-specific volume of interest (VOI), PSS dosimetry provided reliable results. PSS dosimetry was robust in estimating the absorbed dose for the later treatment cycles. Therefore, PSS dosimetry outperformed hybrid dosimetry in terms of dose estimation for a greater number of treatment cycles.

Neovascularization in Outer Membrane of Chronic Subdural Hematoma : A Rationale for Middle Meningeal Artery Embolization.

OBJECTIVE: Chronic subdural hematomas (cSDHs) are generally known to result from traumatic tears of bridging veins. However, the causes of repeat spontaneous cSDHs are still unclear. We investigated the changes in vasculature in the human dura mater and outer membrane (OM) of cSDHs to elucidate the cause of their spontaneous repetition. METHODS: The dura mater was obtained from a normal control participant and a patient with repeat spontaneous cSDHs. The pathological samples from the patient included the dura mater and OM tightly adhered to the inner dura. The samples were analyzed with a particular focus on blood and lymphatic vessels by immunohistochemistry, 3-dimensional imaging using a transparent tissue clearing technique, and electron microscopy. RESULTS: The dural border cell (DBC) layer of the dura mater and OM were histologically indistinguishable. There were 5.9 times more blood vessels per unit volume of tissue in the DBC layer and OM in the patient than in the normal control. The DBC layer and OM contained pathological sinusoidal capillaries not observed in the normal tissue; these capillaries were connected to the middle meningeal arteries via penetrating arteries. In addition, marked lymphangiogenesis in the periosteal and meningeal layers was observed in the patient with cSDHs. CONCLUSION: Neovascularization in the OM seemed to originate from the DBC layer; this is a potential cause of repeat spontaneous cSDHs. Embolization of the meningeal arteries to interrupt the blood supply to pathological capillaries via penetrating arteries may be an effective treatment option.

The Impact of 131I-Metaiodobenzylguanidine as a Conditioning Regimen of Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for High-Risk Neuroblastoma.

BACKGROUND: The optimal conditioning regimen of tandem high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) for high-risk neuroblastoma (HR-NBL) has not been established. The efficacy of 131I-MIBG therapy is under exploration in newly diagnosed HR-NBL patients. Here, we compared the outcomes of tandem HDC/ASCT between the 131I-MIBG combination and non-MIBG groups. METHODS: We retrospectively analyzed the clinical data of 33 HR-NBL patients who underwent tandem HDC/ASCT between 2007 and 2021 at the Seoul National University Children's Hospital. RESULTS: The median age at diagnosis was 3.6 years. 131I-MIBG was administered to 13 (39.4%) of the patients. Thirty patients (90.9%) received maintenance therapy after tandem HDC/ASCT, twenty-two were treated with isotretinoin ± interleukin-2, and eight received salvage chemotherapy. The five-year overall survival (OS) and event-free survival (EFS) rates of all patients were 80.4% and 69.4%, respectively. Comparing the 131I-MIBG combined group and other groups, the five-year OS rates were 82.1% and 79.7% (p = 0.655), and the five-year EFS rates were 69.2% and 69.6% (p = 0.922), respectively. Among the adverse effects of grade 3 or 4, the incidence of liver enzyme elevation was significantly higher in the non-131I-MIBG group. CONCLUSIONS: Although tandem HDC/ASCT showed promising outcomes, the 131I-MIBG combination did not improve survival rates.

Deep Learning-Based Feature Extraction from Whole-Body PET/CT Employing Maximum Intensity Projection Images: Preliminary Results of Lung Cancer Data.

Purpose: Deep learning (DL) has been widely used in various medical imaging analyses. Because of the difficulty in processing volume data, it is difficult to train a DL model as an end-to-end approach using PET volume as an input for various purposes including diagnostic classification. We suggest an approach employing two maximum intensity projection (MIP) images generated by whole-body FDG PET volume to employ pre-trained models based on 2-D images. Methods: As a retrospective, proof-of-concept study, 562 [18F]FDG PET/CT images and clinicopathological factors of lung cancer patients were collected. MIP images of anterior and lateral views were used as inputs, and image features were extracted by a pre-trained convolutional neural network (CNN) model, ResNet-50. The relationship between the images was depicted on a parametric 2-D axes map using t-distributed stochastic neighborhood embedding (t-SNE), with clinicopathological factors. Results: A DL-based feature map extracted by two MIP images was embedded by t-SNE. According to the visualization of the t-SNE map, PET images were clustered by clinicopathological features. The representative difference between the clusters of PET patterns according to the posture of a patient was visually identified. This map showed a pattern of clustering according to various clinicopathological factors including sex as well as tumor staging. Conclusion: A 2-D image-based pre-trained model could extract image patterns of whole-body FDG PET volume by using anterior and lateral views of MIP images bypassing the direct use of 3-D PET volume that requires large datasets and resources. We suggest that this approach could be implemented as a backbone model for various applications for whole-body PET image analyses.

Comparison of the Effects of DOTA and NOTA Chelators on 64Cu-Cudotadipep and 64Cu-Cunotadipep for Prostate Cancer.

BACKGROUND: This study compared the effects of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) as 64Cu-chelating agents in newly developed prostate-specific membrane antigen (PSMA) target compounds, 64Cu-cudotadipep and 64Cu-cunotadipep, on pharmacokinetics. METHODS: The in vitro stability of the chelators was evaluated using human and mouse serum. In vitro PSMA-binding affinity and cell uptake were compared using human 22Rv1 cells. To evaluate specific PSMA-expressing tumor-targeting efficiency, micro-positron emission tomography (mcroPET)/computed tomography (CT) and biodistribution analysis were performed using PSMA+ PC3-PIP and PSMA- PC3-flu tumor xenografts. RESULTS: The serum stability of DOTA- or NOTA-conjugated 64Cu-cudotadipep and 64Cu-cunotadipep was >97%. The Ki value of the NOTA derivative, cunotadipep, in the in vitro affinity binding analysis was higher (2.17 ± 0.25 nM) than that of the DOTA derivative, cudotadipep (6.75 ± 0.42 nM). The cunotadipep exhibited a higher cellular uptake (6.02 ± 0.05%/1 × 106 cells) compared with the cudotadipep (2.93 ± 0.06%/1 × 106 cells). In the biodistribution analysis and microPET/CT imaging, the 64Cu-labeled NOTA derivative, 64Cu-cunotadipep, demonstrated a greater tumor uptake and lower liver uptake than the DOTA derivative. CONCLUSIONS: This study indicates that the PSMA-targeted 64Cu-cunotadipep can be applied in clinical practice owing to its high diagnostic power for prostate cancer.

The role of 99mTc-DPD bone SPECT/CT in the management of growth disturbance of the long bones in pediatric patients: a retrospective observational study.

BACKGROUNDS: Determining the precise localization of diseased physes is crucial for guiding the treatment of growth disturbances. Conventional radiography, computed tomography (CT), and magnetic resonance imaging only provide information on physeal anatomy. Planar bone scintigraphy and bone single-photon emission computed tomography (SPECT) resolutions are suboptimal for clinically managing growth disturbances. Bone SPECT/CT, which provides high-resolution functional information, can be a useful tool for evaluating growth disturbances. The purposes of this study were to identify the conditions in which bone SPECT/CT outperforms planar scintigraphy or SPECT for evaluating the location and activity of diseased physes and to assess surgical outcomes using bone SPECT/CT findings in pediatric patients experiencing long bone growth disturbances. METHODS: Fifty-nine patients who underwent bone SPECT/CT between January 2018 and January 2021 to evaluate physeal activity using technetium-99 m-labeled 2,3-dicarboxypropane-1,1-diphosphonate (99mTc-DPD) were included. The proportions of patients for whom certain modalities provided sufficient data for selecting treatment plans for growth disturbances were compared based on the site of the diseased physis, growth disturbance cause, and shape of deformity (i.e., SPECT/CT vs. planar scintigraphy and SPECT/CT vs. SPECT). For assessing surgical outcomes, progression of post-surgical deformity was investigated by measuring the angles reflecting the degree of deformity, iliac crest height difference, or ulnar variance on radiographs. RESULTS: Bone SPECT/CT was sufficient for selecting a treatment plan, but planar scintigraphy or SPECT alone was insufficient in every 10 patients with diseased physes inside the femoral head (p = 0.002) and in every six with physes that were severely deformed or whose locations were unclear on conventional radiography (p = 0.03). In the proximal or distal tibia, where the tibial and fibular physes often overlapped on planar scintigraphy due to leg rotation, bone SPECT/CT was sufficient in 33/34 patients (97%), but planar scintigraphy and SPECT were sufficient in 10/34 (29%) (p < 0.001) and 24/34 (71%) patients, respectively (p = 0.004). No progression or deformity recurrence occurred. CONCLUSIONS: Bone SPECT/CT may be indicated in proximal femoral growth disturbance, when the physis is unclear on conventional radiography or severely deformed, the leg exhibits rotational deformity, or the patient is noncompliant.

FDG uptake reflects an immune-enriched subtype of thyroid cancer: Clinical implications of imaging-based molecular characterization.

INTRODUCTION: Iodine and FDG uptakes have been established as methods to define the biological properties of thyroid cancer. As various cells in the tumor microenvironment (TME) affect tumor metabolism, we investigated the association between glucose metabolism in thyroid cancer and the TME using transcriptomic analyses. METHODS: We used F-18 FDG PET and RNA sequencing data of thyroid cancer to find associations between TME cell types and glucose metabolism. In addition, publicly available single-cell RNA sequencing data of papillary thyroid cancer was used to investigate glucose metabolism in cell types of the TME. The correlations between the FDG uptake and biological properties of the TME, including glucose metabolism and tumor differentiation score (TDS) were evaluated. Estimation of the proportions of immune and cancer cells (EPIC) was performed. The biological properties of each cell type were also assessed in the single-cell RNA sequencing data. RESULTS: FDG uptake showed a positive correlation with the enrichment score of macrophages and glycolysis activity. In single-cell RNA sequencing, immune cells had both high glucose transporters (GLUTs) and glycolysis signatures, while thyrocytes including cancer cells showed relatively low GLUTs and glycolysis signatures, suggesting that FDG uptake mainly occurred in immune cells of the TME. Moreover, the high GLUTs of myeloid cells were negatively associated with TDS. CONCLUSIONS: Our findings suggest that thyroid cancer with high FDG uptake can be mediated by enriched immune cells of the TME. We suggest that FDG uptake in thyroid cancer could be a marker for the immune-rich type and provide clinical implications for treatment stratification.

Pneumatic Compression-Assisted Lymphoscintigraphy for Quantitative Evaluation of Breast Cancer-Related Lymphedema.

OBJECTIVES: Acquired lymphedema of upper extremity is a chronic pathologic status that frequently occurs after breast cancer treatment. Reliable and quantitative evaluation of lymphedema is crucial for successful management of patients. Although lymphoscintigraphy is the primary investigation for the confirmation and evaluation of lymphedema, the specific protocol of stress intervention is not well established. This study aims to introduce intermittent pneumatic compression (IPC) as a part of stress lymphoscintigraphy and compare the effectiveness of conventional stress lymphoscintigraphy (CSL) and pneumatic compression-assisted lymphoscintigraphy (PCAL). METHODS: Our study was designed as a retrospective analysis of 85 breast cancer patients with lymphedema who underwent lymphoscintigraphy utilizing either IPC device or conventional stress maneuver and received complex decongestive therapy. The flow extent of the lymphatic fluid (FE) was evaluated using a 0- to 4-point scale based on lymphoscintigraphic images. The visualization of lymph nodes was also assessed. The clinical outcomes were evaluated by changes in side-to-side circumferential and volume differences of upper extremities and compared between groups. RESULTS: Of 85 patients, 47 underwent CSL, and 38 underwent PCAL. Participants with relatively preserved flow extent of the lymphatic fluid (FE 3) showed a significant difference in percentage reduction of volume (PRV) between CSL and PCAL groups ( P = 0.036). In the other groups, CSL and PCAL demonstrated comparable differences in PRV without statistical significance. CONCLUSION: Our study suggests that participants in the PCAL group with relatively preserved lymphatic flow extent (FE 3) had better PRV compared with those in the CSL group. The use of IPC devices in lymphoscintigraphy with the novel stress maneuver can help in the quantitative description of lymphedema status and the selection of an appropriate treatment method.

Activated Natural Killer Cell Inoculation Alleviates Fibrotic Liver Pathology in a Carbon Tetrachloride-Induced Liver Cirrhosis Mouse Model.

Activated hepatic stellate cells (HSCs) play a detrimental role in liver fibrosis progression. Natural killer (NK) cells are known to selectively recognize abnormal or transformed cells via their receptor activation and induce target cell apoptosis and, therefore, can be used as a potential therapeutic strategy for liver cirrhosis. In this study, we examined the therapeutic effects of NK cells in the carbon tetrachloride (CCl4)-induced liver cirrhosis mouse model. NK cells were isolated from the mouse spleen and expanded in the cytokine-stimulated culture medium. Natural killer group 2, member D (NKG2D)-positive NK cells were significantly increased after a week of expansion in culture. The intravenous injection of NK cells significantly alleviated liver cirrhosis by reducing collagen deposition, HSC marker activation, and macrophage infiltration. For in vivo imaging, NK cells were isolated from codon-optimized luciferase-expressing transgenic mice. Luciferase-expressing NK cells were expanded, activated and administrated to the mouse model to track them. Bioluminescence images showed increased accumulation of the intravenously inoculated NK cells in the cirrhotic liver of the recipient mouse. In addition, we conducted QuantSeq 3' mRNA sequencing-based transcriptomic analysis. From the transcriptomic analysis, 33 downregulated genes in the extracellular matrix (ECM) and 41 downregulated genes involved in the inflammatory response were observed in the NK cell-treated cirrhotic liver tissues from the 1532 differentially expressed genes (DEGs). This result indicated that the repetitive administration of NK cells alleviated the pathology of liver fibrosis in the CCl4-induced liver cirrhosis mouse model via anti-fibrotic and anti-inflammatory mechanisms. Taken together, our research demonstrated that NK cells could have therapeutic effects in a CCl4-induced liver cirrhosis mouse model. In particular, it was elucidated that extracellular matrix genes and inflammatory response genes, which were mainly affected after NK cell treatment, could be potential targets.

99mTc-MAA accumulation within tumor in preoperative lung perfusion SPECT/CT associated with occult lymph node metastasis in patients with clinically N0 non-small cell lung cancer.

BACKGROUND: 99mTc-MAA accumulation within the tumor representing pulmonary arterial perfusion, which is variable and may have a clinical significance. We evaluated the prognostic significance of 99mTc-MAA distribution within the tumor in non-small cell lung cancer (NSCLC) patients in terms of detecting occult nodal metastasis and lymphovascular invasion, as well as predicting the recurrence-free survival (RFS). METHODS: Two hundred thirty-nine NSCLC patients with clinical N0 status who underwent preoperative lung perfusion SPECT/CT were retrospectively evaluated and classified according to the visual grading of 99mTc-MAA accumulation in the tumor. Visual grade was compared with the quantitative parameter, standardized tumor to lung ratio (TLR). The predictive value of 99mTc-MAA accumulation with occult nodal metastasis, lymphovascular invasion, and RFS was assessed. RESULTS: Eighty-nine (37.2%) patients showed 99mTc-MAA accumulation and 150 (62.8%) patients showed the defect on 99mTc-MAA SPECT/CT. Among the accumulation group, 45 (50.5%) were classified as grade 1, 40 (44.9%) were grade 2, and 4 (4.5%) were grade 3. TLR gradually and significantly increased from grade 0 (0.009 ± 0.005) to grade 1 (0.021 ± 0.005, P < 0.05) and to grade 2-3 (0.033 ± 0.013, P < 0.05). The following factors were significant predictors for occult nodal metastasis in univariate analysis: central location, histology different from adenocarcinoma, tumor size greater than 3 cm representing clinical T2 or higher, and the absence of 99mTc-MAA accumulation within the tumor. Defect in the lung perfusion SPECT/CT remained significant at the multivariate analysis (Odd ratio 3.25, 95%CI [1.24 to 8.48], p = 0.016). With a median follow-up of 31.5 months, the RFS was significantly shorter in the defect group (p = 0.008). Univariate analysis revealed that cell type of non-adenocarcinoma, clinical stage II-III, pathologic stage II-III, age greater than 65 years, and the 99mTc-MAA defect within tumor as significant predictors for shorter RFS. However, only the pathologic stage remained statistically significant, in multivariate analysis. CONCLUSION: The absence of 99mTc-MAA accumulation within the tumor in preoperative lung perfusion SPECT/CT represents an independent risk factor for occult nodal metastasis and is relevant as a poor prognostic factor in clinically N0 NSCLC patients. 99mTc-MAA tumor distribution may serve as a new imaging biomarker reflecting tumor vasculatures and perfusion which can be associated with tumor biology and prognosis.

Voxel-Based Internal Dosimetry for 177Lu-Labeled Radiopharmaceutical Therapy Using Deep Residual Learning.

Purpose: In this study, we propose a deep learning (DL)-based voxel-based dosimetry method in which dose maps acquired using the multiple voxel S-value (VSV) approach were used for residual learning. Methods: Twenty-two SPECT/CT datasets from seven patients who underwent 177Lu-DOTATATE treatment were used in this study. The dose maps generated from Monte Carlo (MC) simulations were used as the reference approach and target images for network training. The multiple VSV approach was used for residual learning and compared with dose maps generated from deep learning. The conventional 3D U-Net network was modified for residual learning. The absorbed doses in the organs were calculated as the mass-weighted average of the volume of interest (VOI). Results: The DL approach provided a slightly more accurate estimation than the multiple-VSV approach, but the results were not statistically significant. The single-VSV approach yielded a relatively inaccurate estimation. No significant difference was noted between the multiple VSV and DL approach on the dose maps. However, this difference was prominent in the error maps. The multiple VSV and DL approach showed a similar correlation. In contrast, the multiple VSV approach underestimated doses in the low-dose range, but it accounted for the underestimation when the DL approach was applied. Conclusion: Dose estimation using the deep learning-based approach was approximately equal to that in the MC simulation. Accordingly, the proposed deep learning network is useful for accurate and fast dosimetry after radiation therapy using 177Lu-labeled radiopharmaceuticals.

Central metabolites and peripheral parameters associated neuroinflammation in fibromyalgia patients: A preliminary study.

To identify central metabolites and peripheral measures associated with neuroinflammation in fibromyalgia (FM), we scanned [11C]-(R)-PK11195 positron emission tomography and magnetic resonance spectroscopy in FM patients. We measured associations between neurometabolite levels measured by magnetic resonance spectroscopy and the extent of neuroinflammation inferred by the distribution volume ratios of [11C]-(R)-PK11195 positron emission tomography in 12 FM patients and 13 healthy controls. We also examined the associations between peripheral parameters, such as creatinine and C-reactive protein, and neuroinflammation. In FM patients, we found negative correlations between neuroinflammation and the creatine (Cr)/total creatine (tCr; Cr + phosphocreatine) ratios in the right (r = -0.708, P = .015) and left thalamus (r = -0.718, P = .008). In FM patients, negative correlations were apparent between neuroinflammation and the glutamate/tCr ratio in the right insula (r = -0.746, P = .005). In FM patients, we found negative correlations between neuroinflammation in the left thalamus (r = -0.601, P = .039) and left insula (r = -0.598, P = .040) and the blood creatinine levels. Additionally, we found significant correlations of other peripheral measures with neuroinflammation in FM patients. Our results suggest that both central metabolites, such as Cr and glutamate, and peripheral creatinine and other parameters are associated with neuroinflammation in patients with FM.

Development and Validation of 18F-FDG PET/CT-Based Models for Predicting Successful Complete Cytoreduction During Primary Cytoreductive Surgery for Advanced Ovarian cancer.

PURPOSE: The aim of this study was to develop an 18F-FDG PET/CT-based model to predict complete cytoreduction during primary cytoreductive surgery (CRS) for ovarian cancer (OC). PATIENTS AND METHODS: We retrospectively identified patients with stage III-IV OC who underwent primary CRS between June 2013 and February 2020 at 2 tertiary centers. Patients from each hospital were assigned to training and test sets. The abdominal cavity was divided into 3 sections, and data for the PET/CT-derived parameters were collected through image analysis. Various prediction models were constructed by combining clinicopathologic characteristics and PET/CT-derived parameters. The performance of the model with the highest area under the receiver operating characteristic curve (AUC) was externally validated. RESULTS: The training and test sets included 159 and 166 patients, respectively. The median age of patients in the test set was 55 years; 72.3% of them had stage III tumors, and 65.4% underwent complete cytoreduction. Metabolic tumor volume, total lesion glycolysis, and the number of metastatic lesions above the upper margin of the renal vein (area A) were selected among the PET/CT parameters. The best predictive multivariable model consisted of CA-125 (<750 or ≥750 IU/mL), number of metastatic lesions (<2 or ≥2), and metabolic tumor volume of area A, predicting complete cytoreduction with an AUC of 0.768. The model was validated using a test set. Its predictive performance yielded an AUC of 0.771. CONCLUSIONS: We successfully developed and validated a preoperative model to predict complete cytoreduction in advanced OC. This model can facilitate patient selection for primary CRS in clinical practice.

Imaging of Indocyanine Green-Human Serum Albumin (ICG-HSA) Complex in Secreted Protein Acidic and Rich in Cysteine (SPARC)-Expressing Glioblastoma.

Glioblastoma is the most common and fatal primary glioma and has a severe prognosis. It is a challenge for neurosurgeons to remove brain tumor tissues completely by resection. Meanwhile, fluorescence-guided surgery (FGS) is a technique used in glioma surgery to enhance the visualization of tumor edges to clarify the extent of tumor resection. Indocyanine green (ICG) is the only FDA-approved NIR fluorescent agent. It non-covalently binds to human serum albumin (HSA). Secreted protein acidic and rich in cysteine (SPARC) is an extracellular glycoprotein expressed in gliomas and binds to albumin, suggesting that it plays an important role in tumor uptake of the ICG-HSA complex. Here we demonstrate the binding properties of HSA or SPARC to ICG using surface plasmon resonance and saturation binding assay. According to in vitro and in vivo studies, the results showed that the uptake of ICG-HSA complex was higher in SPARC-expressing glioblastoma cell line and tumor region compared with the uptake of free ICG. Here, we visualized the SPARC-dependent uptake of ICG and ICG-HSA complex in U87MG. Our results demonstrated that the ICG-HSA complex is likely to be used as an efficient imaging agent targeting SPARC-expressing tumors, especially glioblastoma.

Phase 1 Study of No-Carrier Added 177Lu-DOTATATE (SNU-KB-01) in Patients with Somatostatin Receptor-Positive Neuroendocrine Tumors: The First Clinical Trial of Peptide Receptor Radionuclide Therapy in Korea.

PURPOSE: To provide a wider choice of treatment opportunities for patients with neuroendocrine tumor (NET) in Korea, we have conducted a phase 1, open-label, single-arm, dose-escalation study of SNU-KB-01, a no-carrier added (NCA) 177Lu-labeled DOTATATE. MATERIALS AND METHODS: Seven patients with inoperable, progressive, metastatic, or locally advanced, somatostatin receptor-positive NET with Ki67 index ≤ 20% were enrolled according to the rolling six design. The study consisted of two cohorts to receive 4 cycles of SNU-KB-01 every 8 weeks for the first dose of 5.55 GBq (n=3) and 7.40 GBq (n=4). We assessed the incidence of dose-limiting toxicity (DLT) and adverse event, absorbed dose of kidneys and bone marrow, and objective tumor response. RESULTS: Seven patients completed 4 cycles (21.3-30.1 GBq total dose) of SNU-KB-01. The mean absorbed doses to kidneys and bone marrow were 0.500 mGy/MBq and 0.053 mGy/MBq, respectively, and the total body effective dose was 0.115 mSv/MBq. No DLT was observed and the maximum tolerated dose was 7.40 GBq/cycle. Grade 3 thrombocytopenia occurred in one patient, but no other grade 3 or 4 major hematologic or renal toxicity was observed. The best objective response to SNU-KB-01 was partial response. Overall response rate was 42.9% and disease control rate was 85.7%. CONCLUSION: Treatment with 4 cycles of SNU-KB-01 was well tolerated and resulted in control of disease in most of the patients. Our results indicate SNU-KB-01, an NCA 177Lu-labeled DOTATATE, as a potentially safe and efficacious treatment option for NET patients in Korea.

High intakes of iodine among women during pregnancy and the postpartum period has no adverse effect on thyroid function.

PURPOSE: Given the high consumption of seaweed soup by pregnant and lactating Korean women, concerns have been raised about excessive iodine intake. We evaluated the effects of maternal iodine intake on maternal thyroid function and birth outcomes. We also evaluated iodine intake via seaweed soup during late pregnancy and the early postpartum period. METHODS: A total of 349 pregnant women of the Ideal Breast Milk cohort were recruited in late pregnancy, of whom 302 revisited after delivery. Three-day dietary records were assessed at each visit. Blood was collected for thyroid function test. Obstetrical and birth outcomes were obtained. RESULTS: The median dietary iodine intake was 459 µg/day (interquartile range [IQR] 326.5-647.4 µg/day) during pregnancy. Dietary iodine intake by quartile was not significantly associated with maternal thyroid status, or obstetrical or neonatal outcomes. However, the dietary iodine intake in the early postpartum period was 1759 µg/day (IQR 1026.7-2491.1 µg/day) because of a marked increase in seaweed soup consumption. Of all women, 25.8% consumed seaweed soup more than once over the 3 days of dietary records when pregnant, but the figure rose to 93.4% postpartum. Of postpartum women who consumed seaweed soup daily, the median dietary iodine intakes were 1355, 2394, and 3063 µg/day (soup at one, two, and three-or-four meals). CONCLUSIONS: In these iodine-replete pregnant women, dietary iodine intake during pregnancy showed no effect on maternal thyroid function or birth outcomes. However, iodine intake in the early postpartum period was markedly increased by the frequency of seaweed soup consumption.

Current Status of PSMA-Targeted Radioligand Therapy in the Era of Radiopharmaceutical Therapy Acquiring Marketing Authorization.

Prostate-specific membrane antigen (PSMA) is highly expressed in PCa, which gradually increases in high-grade tumors, metastatic tumors, and tumors nonresponsive to androgen deprivation therapy. PSMA has been a topic of interest during the past decade for both diagnostic and therapeutic targets. Radioligand therapy (RLT) utilizes the delivery of radioactive nuclides to tumors and tumor-associated targets, and it has shown better efficacy with minimal toxicity compared to other systemic cancer therapies. Nuclear medicine has faced a new turning point claiming theranosis as the core of academic identity, since new RLTs have been introduced to clinics through the official new drug development processes for approval from the Food and Drug Administration (FDA) or European Medical Agency. Recently, PSMA targeting RLT was approved by the US FDA in March 2022. This review introduces PSMA RLT focusing on ongoing clinical trials to enhance our understanding of nuclear medicine theranosis and strive for the development of new radiopharmaceuticals.

Reliability and feasibility of visual grading systems and quantitative indexes on [99mTc]Tc-DPD imaging for cardiac amyloidosis.

We aimed to evaluate the reliability and feasibility of visual grading systems and various quantitative indexes of [99mTc]Tc-DPD imaging for cardiac amyloidosis (CA). Patients who underwent [99mTc]Tc-DPD imaging with suspicion of CA were enrolled. On the planar image, myocardial uptake was visually graded using Perugini's and Dorbala's methods (PS and DS). As [99mTc]Tc-DPD indexes, heart-to-whole body ratio (H/WB) and heart-to-contralateral lung ratio (H/CL) were measured on planar image. SUVmax, SUVmean, total myocardial uptake (TMU), and C-index were measured on SPECT/CT. Inter-observer agreement of the indexes and their association with visual grading and clinical factors were evaluated. A total of 152 [99mTc]Tc-DPD images, of which 18 were positive, were analyzed. Inter-observer agreement was high for both DS (κ = 0.95) and PS (κ = 0.96). However, DS showed a higher correlation with quantitative indexes than PS. Inter-observer agreement was also high for SPECT/CT indexes, particularly SUVmax. SUVmax was significantly different between different DS groups (P = 0.014-0.036), and showed excellent correlations with H/WB and H/CL (r = 0.898 and 0.910). SUVmax also showed significant differences between normal, AL, and ATTR pathology (P = 0.022-0.037), and a significant correlation with extracellular volume on cardiac MRI (r = 0.772, P < 0.001). DS is a visual grading system for CA that is more significantly matched with quantitative indexes than PS. SUVmax is a reliable quantitative index on SPECT/CT, with a high inter-observer agreement, correlations with the visual grade, and potential association with cardiac MRI findings.