[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.

Radiation Major Hepatectomy Using Ablative Dose Yttrium-90 Radioembolization in Patients with Hepatocellular Carcinoma 5 cm or Larger.

PURPOSE: To evaluate the safety and effectiveness of ablative radioembolization for large hepatocellular carcinoma (HCC) while preserving a small future liver remnant (FLR). MATERIALS AND METHODS: Twenty-five patients with large HCC of ≥5 cm requiring treatment for >60% of the total liver volume and having well-preserved liver function were treated with ablative glass microsphere radioembolization at a single institution from January 2017 to December 2021. Radioembolization was performed with a mean absorbed dose of >150 Gy, and the FLR per nontumor liver volume (NTLV) was set at >30%. Changes in liver function, adverse events, duration of response (DoR) in a treated area, time-to-progression (TTP), and overall survival (OS) were retrospectively investigated. RESULTS: The largest tumor diameter and planned dose per treated volume were 11.4 cm ± 3.9 and 242.3 Gy ± 63.6 (169.4 Gy ± 45.9 per whole liver volume), respectively. All patients remained at Child-Pugh Class A for 90 days. No patient experienced Grade 3‒4 hyperbilirubinemia or new ascites. One patient (lung dose, 27.8 Gy) developed radiation pneumonitis requiring transient steroid treatment. According to the posttreatment dosimetry, the tumorous and nontumorous liver absorbed doses were 418.8 Gy ± 227.4 and 69.0 Gy ± 32.1, respectively. The median DoR in a treated area and TTP were 22.0 and 17.1 months, respectively. The 5-year OS rate was 83.2%. CONCLUSIONS: Ablative radioembolization of large HCC of ≥5 cm can be performed safely and effectively in patients with preserved liver function when FLR/NTLV exceeds 30%.

Intrathecal [64Cu]Cu-albumin PET reveals age-related decline of lymphatic drainage of cerebrospinal fluid.

Age-related cognitive decline is associated with dysfunctional lymphatic drainage of cerebrospinal fluid (CSF) through meningeal lymphatic vessels. In this study, intrathecal [64Cu]Cu-albumin positron emission tomography (PET) was applied in mice to evaluate lymphatic drainage of CSF and its variation with age. [64Cu]Cu-albumin PET was performed at multiple time points after intrathecal injection of [64Cu]Cu-albumin at an infusion rate of 700 nl/min in adult and aged mice (15-25 months old). CSF clearance and paravertebral lymph nodes were quantified after injection and during the stationary phase. Stationary phase of the next day followed the initial perturbed state by injection of 6 ul (1/7 of total CSF volume) and CSF clearance half-time from the subarachnoid space was 93.4 ± 19.7 and 123.3 ± 15.6 min in adult and aged mice (p = 0.01), respectively. While the % injected dose of CSF space were higher, the activity of the paravertebral lymph nodes were lower in the aged mice on the next day. [64Cu]Cu-albumin PET enabled us to quantify CSF-lymphatic drainage across all levels of brain spinal cords and to visualize and quantify lymph node activity due to CSF drainage. [64Cu]Cu-albumin PET revealed the age-related decrease of the lymphatic drainage of CSF due to this decreased drainage from the subarachnoid space, especially during the stationary phase, in aged mice.

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.

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.

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.

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.

Circulation Time-Optimized Albumin Nanoplatform for Quantitative Visualization of Lung Metastasis via Targeting of Macrophages.

The development of molecular imaging probes to identify key cellular changes within lung metastases may lead to noninvasive detection of metastatic lesions in the lung. In this study, we constructed a macrophage-targeted clickable albumin nanoplatform (CAN) decorated with mannose as the targeting ligand using a click reaction to maintain the intrinsic properties of albumin in vivo. We also modified the number of mannose molecules on the CAN and found that mannosylated serum albumin (MSA) harboring six molecules of mannose displayed favorable pharmacokinetics that allowed high-contrast imaging of the lung, rendering it suitable for in vivo visualization of lung metastases. Due to the optimized control of functionalization and surface modification, MSA enhanced blood circulation time and active/passive targeting abilities and was specifically incorporated by mannose receptor (CD206)-expressing macrophages in the metastatic lung. Moreover, extensive in vivo imaging studies using single-photon emission computed tomography (SPECT)/CT and positron emission tomography (PET) revealed that blood circulation of time-optimized MSA can be used to discern metastatic lesions, with a strong correlation between its signal and metastatic burden in the lung.

Phase I Clinical Trial of Prostate-Specific Membrane Antigen-Targeting 68Ga-NGUL PET/CT in Healthy Volunteers and Patients with Prostate Cancer.

OBJECTIVE: 68Ga-NGUL is a novel prostate-specific membrane antigen (PSMA)-targeting tracer based on Glu-Urea-Lys derivatives conjugated to a 1,4,7-triazacyclononane-N, N', N″-triacetic acid (NOTA) chelator via a thiourea-type short linker. This phase I clinical trial of 68Ga-NGUL was conducted to evaluate the safety and radiation dosimetry of 68Ga-NGUL in healthy volunteers and the lesion detection rate of 68Ga-NGUL in patients with prostate cancer. MATERIALS AND METHODS: We designed a prospective, open-label, single-arm clinical trial with two cohorts comprising six healthy adult men and six patients with metastatic prostate cancer. Safety and blood test-based toxicities were monitored throughout the study. PET/CT scans were acquired at multiple time points after administering 68Ga-NGUL (2 MBq/kg; 96-165 MBq). In healthy adults, absorbed organ doses and effective doses were calculated using the OLINDA/EXM software. In patients with prostate cancer, the rates of detecting suspicious lesions by 68Ga-NGUL PET/CT and conventional imaging (CT and bone scintigraphy) during the screening period, within one month after recruitment, were compared. RESULTS: All 12 participants (six healthy adults aged 31-32 years and six prostate cancer patients aged 57-81 years) completed the clinical trial. No drug-related adverse events were observed. In the healthy adult group, 68Ga-NGUL was rapidly distributed, with the highest uptake in the kidneys. The median effective dose coefficient was calculated as 0.025 mSv/MBq, and cumulative activity in the bladder had the highest contribution. In patients with metastatic prostate cancer, 229 suspicious lesions were detected using either 68Ga-NGUL PET/CT or conventional imaging. Among them, 68Ga-NGUL PET/CT detected 199 (86.9%) lesions and CT or bone scintigraphy detected 114 (49.8%) lesions. CONCLUSION: 68Ga-NGUL can be safely applied clinically and has shown a higher detection rate for the localization of metastatic lesions in prostate cancer than conventional imaging. Therefore, 68Ga-NGUL is a valuable option for prostate cancer imaging.

[ 64Cu]Cu-Albumin Clearance Imaging to Evaluate Lymphatic Efflux of Cerebrospinal Space Fluid in Mouse Model.

Purpose: Clearance of brain waste in the cerebrospinal fluid (CSF) through the meningeal lymphatic vessels (mLV) has been evaluated mostly through the fluorescent imaging which has inherent limitations in the context of animal physiology and clinical translatability. The study aimed to establish molecular imaging for the evaluation of mLV clearance function. Methods: Radionuclide imaging after intrathecal (IT) injection was acquired in C57BL/6 mice of 2-9 months. The distribution of [99mTc]Tc-diethylenetriamine pentaacetate (DTPA) and [64Cu]Cu-human serum albumin (HSA) was comparatively evaluated. Evans Blue and [64Cu]Cu-HSA were used to evaluate the distribution of tracer under various speed and volume conditions. Results: [99mTc]Tc-DTPA is not a suitable tracer for evaluation of CSF clearance via mLV as no cervical lymph node uptake was observed while it was cleared from the body. A total volume of 3 to 9 µL at an infusion rate of 300 to 500 nL/min was not sufficient for the tracer to reach the cranial subarachnoid space and clear throughout the mLV. As a result, whole-body positron emission tomography imaging using [64Cu]Cu-HSA at 700 nL/min, to deliver 6 µL of injected volume, was set for characterization of the CSF to mLV clearance. Through this protocol, the mean terminal CSF clearance half-life was measured to be 123.6 min (range 117.0-135.0) in normal mice. Conclusions: We established molecular imaging to evaluate CSF drainage through mLV using [64Cu]Cu-HSA. This imaging method is expected to be extended in animal models of dysfunctional meningeal lymphatic clearance and translational research for disease-modifying therapeutic approaches. Supplementary Information: The online version contains supplementary material available at 10.1007/s13139-022-00746-6.

Head-to-Head Comparison of 68Ga-NOTA (68Ga-NGUL) and 68Ga-PSMA-11 in Patients with Metastatic Prostate Cancer: A Prospective Study.

68Ga-NOTA Glu-Urea-Lys (NGUL) is a novel prostate-specific membrane antigen (PSMA)-targeting tracer used for PET/CT imaging. This study aimed to compare performance in the detection of primary and metastatic lesions and to compare biodistribution between 68Ga-NGUL and 68Ga-PSMA-11 in the same patients with prostate cancer. Methods: Eleven patients with metastatic prostate cancer were prospectively recruited. The quantitative tracer uptake was determined in normal organs and in primary and metastatic lesions. Results:68Ga-NGUL showed significantly lower normal-organ uptake and rapid urinary clearance. The number and sites of detected PSMA-positive primary and metastatic lesions were identical, and no significant quantitative uptake difference was observed. 68Ga-NGUL showed a relatively lower tumor-to-background ratio than 68Ga-PSMA-11. Conclusion: In a head-to-head comparison with 68Ga-PSMA-11, 68Ga-NGUL showed lower uptake in normal organs and similar performance in detecting PSMA-avid primary and metastatic lesions. 68Ga-NGUL could be a valuable option for PSMA imaging.

Brain Glymphatic/Lymphatic Imaging by MRI and PET.

Since glymphatic was proposed and meningeal lymphatic was discovered, MRI and even PET were introduced to investigate brain parenchymal interstitial fluid (ISF), cerebrospinal fluid (CSF), and lymphatic outflow in rodents and humans. Previous findings by ex vivo fluorescent microscopic, and in vivo two-photon imaging in rodents were reproduced using intrathecal contrast (gadobutrol and the similar)-enhanced MRI in rodents and further in humans. On dynamic MRI of meningeal lymphatics, in contrast to rodents, humans use mainly dorsal meningeal lymphatic pathways of ISF-CSF-lymphatic efflux. In mice, ISF-CSF exchange was examined thoroughly using an intra-cistern injection of fluorescent tracers during sleep, aging, and neurodegeneration yielding many details. CSF to lymphatic efflux is across arachnoid barrier cells over the dorsal dura in rodents and in humans. Meningeal lymphatic efflux to cervical lymph nodes and systemic circulation is also well-delineated especially in humans onintrathecal contrast MRI. Sleep- or anesthesia-related changes of glymphatic-lymphatic flow and the coupling of ISF-CSF-lymphatic drainage are major confounders ininterpreting brain glymphatic/lymphatic outflow in rodents. PET imaging in humans should be interpreted based on human anatomy and physiology, different in some aspects, using MRI recently. Based on the summary in this review, we propose non-invasive and longer-term intrathecal SPECT/PET or MRI studies to unravel the roles of brain glymphatic/lymphatic in diseases.

Unsupervised clustering of dopamine transporter PET imaging discovers heterogeneity of parkinsonism.

Parkinsonism has heterogeneous nature, showing distinctive patterns of disease progression and prognosis. We aimed to find clusters of parkinsonism based on 18 F-fluoropropyl-carbomethoxyiodophenylnortropane (FP-CIT) PET as a data-driven approach to evaluate heterogenous dopaminergic neurodegeneration patterns. Two different cohorts of patients who received FP-CIT PET were collected. A labeled cohort (n = 94) included patients with parkinsonism who underwent a clinical follow-up of at least 3 years (mean 59.0 ± 14.6 months). An unlabeled cohort (n = 813) included all FP-CIT PET data of a single-center. All PET data were clustered by a dimension reduction method followed by hierarchical clustering. Four distinct clusters were defined according to the imaging patterns. When the diagnosis of the labeled cohort of 94 patients was compared with the corresponding cluster, parkinsonism patients were mostly included in two clusters, cluster "0" and "2." Specifically, patients with progressive supranuclear palsy were significantly more included in cluster 0. The two distinct clusters showed significantly different clinical features. Furthermore, even in PD patients, two clusters showed a trend of different clinical features. We found distinctive clusters of parkinsonism based on FP-CIT PET-derived heterogeneous neurodegeneration patterns, which were associated with different clinical features. Our results support a biological underpinning for the heterogeneity of neurodegeneration in parkinsonism.

A pan-cancer analysis of the clinical and genetic portraits of somatostatin receptor expressing tumor as a potential target of peptide receptor imaging and therapy.

PURPOSE: Although somatostatin receptor (SST) is a promising theranostic target and is widely expressed in tumors of various organs, the indication for therapies targeting SST is limited to typical gastroenteropancreatic neuroendocrine tumors (NETs). Thus, broadening the scope of the current clinical application of peptide receptor radiotherapy (PRRT) can be supported by a better understanding of the landscape of SST-expressing tumors. METHODS: SST expression levels were assessed in data from The Cancer Genome Atlas across 10,701 subjects representing 32 cancer types. As the major target of PRRT is SST subtype 2 (SST2), correlation analyses between the pan-cancer profiles, including clinical and genetic features, and SST2 level were conducted. The median SST2 expression level of pheochromocytoma and paraganglioma (PCPG) samples was used as the threshold to define "high-SST2 tumors." The prognostic value of SST2 in each cancer subtype was evaluated by using Cox proportional regression analysis. RESULTS: We constructed a resource of SST expression patterns associated with clinicopathologic features and genomic alterations. It provides an interactive tool to analyze SST expression patterns in various cancer types. As a result, eight of the 31 cancer subtypes other than PCPG had more than 5% of tumors with high-SST2 expression. Low-grade glioma (LGG) showed the highest proportion of high-SST2 tumors, followed by breast invasive carcinoma (BRCA). LGG showed different SST2 levels according to tumor grade and histology. IDH1 mutation was significantly associated with high-SST2 status. In BRCA, the SST2 level was different according to the hormone receptor status. High-SST2 status was significantly associated with good prognosis in LGG patients. High-SST2 status showed a trend for association with poor prognosis in triple-negative breast cancer subjects. CONCLUSION: A broad range of SST2 expression was observed across diverse cancer subtypes. The SST2 expression level showed a significant association with genomic and clinical aspects across cancers, especially in LGG and BRCA. These findings extend our knowledge base to diversify the indications for PRRT as well as SST imaging.

Assessment of Inflammation in Pulmonary Artery Hypertension by 68Ga-Mannosylated Human Serum Albumin.

Rationale: Diagnosis and monitoring of patients with pulmonary artery hypertension (PAH) is currently difficult.Objectives: We aimed to develop a noninvasive imaging modality for PAH that tracks the infiltration of macrophages into the pulmonary vasculature, using a positron emission tomography (PET) agent, 68Ga-2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) mannosylated human serum albumin (MSA), that targets the mannose receptor (MR).Methods: We induced PAH in rats by monocrotaline injection. Tissue analysis, echocardiography, and 68Ga-NOTA-MSA PET were performed weekly in rats after monocrotaline injection and in those treated with either sildenafil or macitentan. The translational potential of 68Ga-NOTA-MSA PET was explored in patients with PAH.Measurements and Main Results: Gene sets related to macrophages were significantly enriched on whole transcriptome sequencing of the lung tissue in PAH rats. Serial PET images of PAH rats demonstrated increasing uptake of 68Ga-NOTA-MSA in the lung by time that corresponded with the MR-positive macrophage recruitment observed in immunohistochemistry. In sildenafil- or macitentan-treated PAH rats, the infiltration of MR-positive macrophages by histology and the uptake of 68Ga-NOTA-MSA on PET was significantly lower than that of the PAH-only group. The pulmonary uptake of 68Ga-NOTA-MSA was significantly higher in patients with PAH than normal subjects (P = 0.009) or than those with pulmonary hypertension by left heart disease (P = 0.019) (n = 5 per group).Conclusions:68Ga-NOTA-MSA PET can help diagnose PAH and monitor the inflammatory status by imaging the degree of macrophage infiltration into the lung. These observations suggest that 68Ga-NOTA-MSA PET has the potential to be used as a novel noninvasive diagnostic and monitoring tool of PAH.

Anatomical attributes of clinically relevant diagonal branches in patients with left anterior descending coronary artery bifurcation lesions.

AIMS: This study aimed to investigate the anatomical attributes determining myocardial territory of diagonal branches and to develop prediction models for clinically relevant branches using myocardial perfusion imaging (MPI) and coronary CT angiography (CCTA). METHODS AND RESULTS: The amount of ischaemia and subtended myocardial mass of diagonal branches was quantified using MPI by percent ischaemic myocardium (%ischaemia) and CCTA by percent fractional myocardial mass (%FMM), respectively. In 49 patients with isolated diagonal branch disease, the mean %ischaemia by MPI was 6.8±4.0%, whereas in patients with total occlusion or severe disease of all diagonal branches it was 8.4±3.3%. %ischaemia was different according to the presence of non-diseased diagonal branches and dominant left circumflex artery (LCx). In the CCTA cohort (306 patients, 564 diagonal branches), mean %FMM was 5.9±4.4% and 86 branches (15.2%) had %FMM ≥10%. %FMM was different according to LCx dominance, number of branches, vessel size, and relative dominance between two diagonal branches. The diagnostic accuracy of prediction models for %FMM ≥10% based on logistic regression and decision tree was 0.92 (95% CI: 0.85-0.96) and 0.91 (95% CI: 0.84-0.96), respectively. There was no difference in the diagnostic performance of models with and without size criterion. CONCLUSIONS: LCx dominance, number of branches, vessel size, and dominance among diagonal branches determined the myocardial territory of diagonal branches. Clinical application of prediction models based on these anatomical attributes can help to determine the clinically relevant diagonal branches in the cardiac catheterisation laboratory. CLINICAL TRIAL REGISTRATION: NCT03935542