Efficacy of preoperative lymphoscintigraphy in predicting surgical outcomes of lymphaticovenous anastomosis in lower extremity lymphedema: Clinical correlations in gynecological cancer-related lymphedema.

BACKGROUND: Lymphaticovenous anastomosis (LVA) is a promising microsurgical treatment for lower extremity lymphedema (LEL). Lymphoscintigraphy effectively assesses lower limb lymphatic systems before LVA, but its role in predicting the therapeutic outcomes of LVA is indeterminate. In this study we investigate the efficacy of preoperative lymphoscintigraphy using clinical findings to predict outcomes in gynecological cancer-related LEL patients who underwent LVA. METHODS: A retrospective review was conducted on consecutive gynecological cancer patients with LEL who had undergone LVA between June 2018 and June 2021. The therapeutic efficacy was assessed by measuring the change rate of the lower extremity lymphedema index (LELi) six months after surgery. Clinical data and lymphoscintigraphic findings were analyzed to assess therapeutic efficacy of LVA. RESULTS: Out of the 60 evaluated legs, 83.3% of the legs showed improved results after LVA. Univariable linear regression analysis revealed that higher preoperative LELi, and ovarian cancer were associated with superior LELi change rate (LC rate). Absence of dermal backflow (DBF) on lymphoscintigraphy was associated with inferior LC rate. Multivariable linear regression analysis identified ovarian cancer and higher preoperative LELi were independently correlated with favorable outcomes, while the absence of DBF was independently correlated with inferior outcomes. CONCLUSION: The results of this study emphasizes the effectiveness of preoperative lymphoscintigraphy, preoperative LELi, and primary malignancy as predictors of LVA outcomes in gynecological cancer-related LEL patients.

Saengmaeksan, a traditional polyherbal formulation containing Panax ginseng, improves energy metabolism during exercise.

Saengmaeksan (SMS), a representative oriental medicine that contains Panax ginseng Meyer, Liriope muscari, and Schisandra chinensis (1:2:1), is used to improve body vitality and enhance physical activity. However, there is limited scientific evidence to validate the benefits of SMS. Here, we investigated the in vitro and in vivo regulatory effects of SMS and its constituents on energy metabolism and the underlying molecular mechanisms. For this, quantitative real-time polymerase chain reaction, 3D holotomographic microscopy, western blotting, and glucose uptake experiments using 18F-fluoro-2-deoxy-D-glucose (18F-FDG) were performed using L6 cells to investigate in vitro energy metabolism changes. In addition, 18F-fluorocholine (18F-FCH) and 18F-FDG positron emission tomography/computed tomography (PET/CT) analyses, immunohistochemistry, and respiratory gas analysis were performed in mice post-endurance exercise on a treadmill. In the energy metabolism of L6 cells, a significant reversal in glucose uptake was observed in the SMS-treated group, as opposed to an increase in uptake over time compared to the untreated control group. Furthermore, P. ginseng alone and SMS significantly decreased the volume of lipid droplets. SMS also regulated the phosphorylation of extracellular signal-regulated kinase (ERK), phosphorylation of p38, mitochondrial morphology, and the expression of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE/Ref-1) in H2O2-stimulated L6 cells. In addition, SMS treatment was found to regulate whole body and muscle energy metabolism in rats subjected to high-intensity exercise, as well as glucose and lipid metabolism in skeletal muscle. Therefore, SMS containing P. ginseng ameliorated imbalanced energy metabolism through oxidative stress-induced APE/Ref-1 expression. SMS may be a promising supplemental option for metabolic performance.

Value of Quantitative Salivary Gland SPECT/CT for the Detection of Saliva Leakage.

ABSTRACT: A 47-year-old woman presented to our emergency department with a 10-day history of pain, halitosis, and swelling below the left jaw. The patient was diagnosed with left sialadenitis and left submandibular abscess by tissue biopsy. An otolaryngologist performed transcervical incision and drainage of the abscess 1 day after admission. Postoperatively, the patient complained of a sensation of fluid leakage from the mouth, and a continuous purulent discharge was observed. One month postoperatively, a salivary gland scan and SPECT/CT were performed to investigate the sialorrhea and the cause of the discharge. Salivary gland SPECT/CT images localized the saliva leakage site.

The added value of SPECT/CT lymphoscintigraphy in the initial assessment of secondary extremity lymphedema patients.

An added value of SPECT/CT over planar lymphoscintigraphy for initial staging in patients with secondary extremity lymphedema was investigated. Furthermore, we developed a hybrid SPECT/CT classification combining dermal backflow (DBF) of SPECT and honeycomb pattern (HP) of CT, correlated it with lymphoscintigraphic staging and clinical severity. Forty-one patients with secondary extremity lymphedema who underwent lymphoscintigraphy with SPECT/CT were included retrospectively. The severity of extremity lymphedema was assessed using CT volumetry. Lymphoscintigraphic findings were evaluated using the Taiwan Lymphoscintigraphy Staging (TLS), and CT-based and SPECT-based quantitative analysis were performed. TLS was performed by planar scintigraphy only and with SPECT/CT, respectively. The SPECT/CT findings were classified into DBF-/HP-, DBF+/HP-, DBF+/HP+, and DBF-/HP+. Based on these findings, patients were categorized into five classes: Class 1 = DBF-HP- entire limb, Class 2 = DBF+/HP- proximal/distal limb without DBF+/HP+ or DBF-/HP+, Class 3 = DBF+/HP+ proximal/distal limb without DBF-/HP+, Class 4 = Mixed DBF+/HP+ and DBF-/HP+ in proximal/distal limb, Class 5 = DBF-/HP+ entire limb. Adding SPECT/CT to planar scintigraphy showed a 15.4% modification rate in lymphoscintigraphic staging. HP volume ratio significantly increased as clinical severity and lymphoscintigraphic staging increased, while DBF volume ratio increased with severity and followed expected patterns according to lymphoscintigraphic staging. Hybrid SPECT/CT lymphoscintigraphic classification showed strong positive correlation with clinical severity and TLS. Our results demonstrated substantial modification of lymphoscintigraphic staging by adding SPECT/CT to a conventional planar scintigraphy. In addition, a hybrid SPECT/CT is expected to provide new indicators reflecting lymphoscintigraphic staging and clinical severity by providing both of functional DBF and anatomical HP information.

A novel chalcone derivative exerts anticancer effects by promoting apoptotic cell death of human pancreatic cancer cells.

Aggressive pancreatic cancer is typically treated using chemotherapeutics to reduce the tumor pre-operatively and prevent metastasis post-operatively, as well as surgical approaches. In the present study, we synthesized a hydroxyl group-introduced chalcone derivative (1, IC50 = 32.1 µM) and investigated its potential as an anticancer drug candidate by evaluating its apoptosis-promoting effects on BXPC-3 cancer cells. The viability of BXPC-3 cells treated with 1 was measured using the water-soluble tetrazolium 1 reagent. BXPC-3 cells induced by 1 were stained with diverse probes or antibodies, such as ethidium homodimer-1, Hoechst, anti-Ki67, and MitoTracker. Protein expression was measured using an immunoblotting assay, and mRNA expression was determined using real-time polymerase chain reaction. Apoptotic molecular features, such as lipid accumulation and protein degradation, were monitored directly using stimulated Raman scattering microspectroscopy. Through incubation time- and concentration-dependent studies of 1, we found that it significantly reduced the proliferation and increased the number of apoptotic BXPC-3 cells. Compound 1 induced mitochondrial dysfunction, phosphorylation of p38, and caspase 3 cleavage. These results indicate that 1 is a potential therapeutic agent for pancreatic cancer, providing valuable insights into the development of new anticancer drug candidates.

Salivary Gland Uptake on 18F-FP-CIT PET as a New Biomarker in Patients With Parkinsonism.

OBJECTIVE: 18F-FP-CIT positron emission tomography (PET) is known for its high sensitivity and specificity for evaluating striatal dopamine transporter (DAT) binding. Recently, for the early diagnose of Parkinson's disease, many researchers focused on the diagnosis of synucleinopathy in organs involved in non-motor symptoms of Parkinson's disease. We investigated the feasibility of salivary gland uptake on 18F-FP-CIT PET as a new biomarker in patients with parkinsonism. MATERIALS AND METHODS: A total of 219 participants with confirmed or presumed parkinsonism, including 54 clinically diagnosed idiopathic Parkinson's disease (IPD), 59 suspected and yet undiagnosed, and 106 with secondary parkinsonism, were enrolled. The standardized uptake value ratio (SUVR) of the salivary glands was measured on both early and delayed 18F-FP-CIT PET scans using the cerebellum as the reference region. Additionally, the delayed-to-early ratio (DE_ratio) of salivary gland was obtained. The results were compared between patients with different PET patterns. RESULTS: The SUVR in early 18F-FP-CIT PET scan was significantly higher in patients with IPD pattern compared that in the non-dopaminergic degradation group (0.5 ± 0.19 vs. 0.6 ± 0.21, P < 0.001). Compared with the non-dopaminergic degradation group, the DE_ratio was significantly lower in patients with IPD (5.05 ± 1.7 vs. 4.0 ± 1.31, P < 0.001) or atypical parkinsonism patterns (5.05 ± 1.7 vs. 3.76 ± 0.96, P < 0.05). The DE_ratio was moderately and positively correlated with striatal DAT availability in both the whole striatum (r = 0.37, P < 0.001) and posterior putamen (r = 0.36, P < 0.001). CONCLUSION: Parkinsonism patients with an IPD pattern exhibited a significant increase in uptake on early 18F-FP-CIT PET and a decrease in the DE_ratio in the salivary gland. Our findings suggest that salivary gland uptake of dual-phase 18F-FP-CIT PET can provide diagnostic information on DAT availability in patients with Parkinson's disease.

In vivo tissue pharmacokinetics of ERBB2-specific binding oligonucleotide-based drugs by PET imaging.

Although aptamers have shown excellent target specificity in preclinical and clinical studies either by themselves or as aptamer-drug conjugates, their in vivo tissue pharmacokinetic (PK) analysis is still problematic. We aimed to examine the utility of image-based positron emission tomography (PET) to evaluate in vivo tissue PK, target specificity, and applicability of oligonucleotides. For this, fluorine-18-labeled aptamers with erb-b2 receptor tyrosine kinase 2 (ERBB2)-specific binding were synthesized by base-pair hybridization using a complementary oligonucleotide platform. To investigate the PKs and properties of in vivo tissue, usefulness of in vivo PET imaging in the development of an oligonucleotide-based drug as an assessment tool was evaluated in normal and tumor xenografted mice. ERBB2-cODN-idT-APs-[18 F]F ([18 F]1), injected intravenously showed significant and rapid uptake in most tissues except for the initial brain and muscle; the uptake was highest in the heart, followed by kidneys, liver, lungs, gall bladder, spleen, and stomach. The main route of excretion was through the renal tract ~77.8%, whereas about 8.3% was through the biliary tract of the total dose. The estimated effective dose for an adult woman was 0.00189 mGy/MBq, which might be safe. ERBB2-positive tumor could be well visualized in the KPL4 xenograft animal model by in vivo PET imaging. Consequently, the distribution in each organ including ERBB2 expression could be well determined and quantified by PET with fluorine-18-labeled aptamers. In vivo PK parameters such as terminal half-life, time to maximum concentration, area under the curve, and maximum concentration, were also successfully estimated. These results suggest that image-based PET with radioisotope-labeled aptamers could be provide valuable information on properties of oligonucleotide-based drugs in drug discovery of targeted therapeutics against various diseases.

Clinical Impact of SPECT/CT in Evaluation of Abdominothoracic Fistula.

ABSTRACT: Abdominothoracic fistula is rarely observed but can be life-threatening. Pleuroperitoneal communication, known to occur in 1.6% of all patients who undergo continuous ambulatory peritoneal dialysis, is an uncommon but well-recognized complication. The most common symptoms are dyspnea and right-sided pleural effusion. A biliopleural fistula is well-described as a complication of radiofrequency ablation and transcatheter arterial chemoembolization of hepatic lesions. It is important to diagnose the cause of pleural effusion early for proper treatment because if the abdominothoracic fistula effusion amount is not large, appropriate diagnosis may be difficult. Here, we introduce 2 cases showing the usefulness of SPECT/CT in evaluating pleuroperitoneal and biliopleural fistulas.

Potential Utility of SPECT/CT for Early Detection of Spontaneous Osteonecrosis of the Knee.

ABSTRACT: Spontaneous osteonecrosis of the knee (SONK) is the most common phenotype of osteonecrosis of knee joints in older adults. Early diagnosis with appropriate management is crucial for improving the prognosis of the SONK. We present SONK in bone scintigraphy and SPECT/CT in 65-year-old man with sudden worsening knee pain and normal radiographs. SPECT/CT revealed intense uptake in subchondral area of left femoral medial condyle, which can be differed from progressed osteoarthritic change of the knee joints suspected on planar scintigraphy. Subsequently performed MRI showed characteristic finding of SONK. Total knee replacement arthroplasty was performed with final histological diagnosis of SONK.

Feasibility of 18F-Fluorocholine PET for Evaluating Skeletal Muscle Atrophy in a Starved Rat Model.

Imaging techniques for diagnosing muscle atrophy and sarcopenia remain insufficient, although various advanced diagnostic methods have been established. We explored the feasibility of 18F-fluorocholine (18F-FCH) positron emission tomography/computed tomography (PET/CT) for evaluating skeletal muscle atrophy, as an imaging technique that tracks choline level changes in muscles. Cell uptake in L6 cells by 18F-FCH was performed in a complete medium containing serum (untreated group, UN) and a serum-free medium (starved group, ST). Small-animal-dedicated PET/CT imaging with 18F-FCH was examined in in-vivo models with rats that were starved for 2 days to cause muscle atrophy. After the hind limbs were dissected, starvation-induced in-vivo models were anatomically confirmed by reverse-transcription polymerase chain reaction to evaluate the expression levels of the atrophy markers muscle RING-finger protein-1 (MuRF-1) and atrogin-1. 18F-FCH uptake was lower in the starvation-induced cells than in the untreated group, and in-vivo PET uptake also revealed a similar tendency (the average standardized uptake value (SUVmean) = 0.26 ± 0.06 versus 0.37 ± 0.07, respectively). Furthermore, the expression levels of MuRF-1 and atrogin-1 mRNA were significantly increased in the starvation-induced muscle atrophy of rats compared to the untreated group. 18F-FCH PET/CT may be a promising tool for diagnosing skeletal muscle atrophy.

Clinical Usefulness of 18 F-FET PET in a Pediatric Patient With Suspected Demyelinating Disease.

ABSTRACT: An 11-year-old boy who presented with headache and progressive right-sided weakness exhibited cortical swelling in the parafalcine area of both frontoparietal high convexity and splenium portion of corpus callosum on brain MRI. This suggested the possibility of encephalopathy, but required differential diagnosis from brain tumor. 18 F-FET ( O -(2-[ 18 F]fluoroethyl)- l -tyrosine) PET/CT identified increased uptake along the parafalcine area of the frontoparietal lobes and the splenium portion of the corpus callosum. The relatively low target-to-background ratios were more indicative of inflammatory changes such as demyelinating disease. The patient recovered after empirical steroid and immunoglobulin treatment. Clinically, the patient was diagnosed with acute disseminated encephalomyelitis.

Effects of taurine and ginseng extracts on energy metabolism during exercise and their anti-fatigue properties in mice.

BACKGROUND/OBJECTIVES: Ginseng extract (GSE) and taurine (TR) are widely used antifatigue resources in functional foods. However, the mechanism underlying the antifatigue effects of GSE and TR are still unclear. Hence, we investigated whether GSE and TR have synergistic effects against fatigue in mice. MATERIALS/METHODS: L6 cells were treated with different concentrations of TR and GSE, and cell viability was determined using 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium. Oxidative stress was analyzed by immunocytochemistry using MitoTracker™ Red FM and an anti-8-oxoguanine antibody. Respiratory gas analysis was performed to investigate metabolism. Expression of an activated protein kinase was analyzed using immunohistochemistry. Gene expression of cluster of differentiation 36 and pyruvate dehydrogenase lipoamide kinase isozyme 4 was measured using reverse transcription-polymerase chain reaction. Mice were orally administered TR, GSE, or their combination for 30 days, and then fatigue-related parameters, including lactate, blood urea nitrogen, and glycogen, were measured after forced swimming. RESULTS: TR and GSE reduced oxidative stress levels in hydrogen peroxide-stimulated L6 cells and enhanced the oxygen uptake and lipid metabolism in mice after acute exercise. After oral administration of TR or GSE for 30 days, the fatigue-related parameters did not change in mice. However, the mice administered GSE (400 mg/kg/day) alone for 30 days could swim longer than those from the other groups. Further, no synergistic effect was observed after the swimming exercise in mice treated with the TR and GSE combination for 30 days. CONCLUSIONS: Taken together, our data suggest that TR and GSE may exert antifatigue effects in mice after acute exercise by enhancing oxygen uptake and lipid oxidation.

Potential anticancer effect of aspirin and 2'-hydroxy-2,3,5'-trimethoxychalcone-linked polymeric micelles against cervical cancer through apoptosis.

Although early diagnosis and treatment of cancers in women are achievable through continuous diagnostic tests, cervical cancer (CVC) still has a high mortality rate. In the present study, we investigated whether certain nanoparticles (NPs), comprising aspirin conjugated 2'-hydroxy-2,3,5'-trimethoxychalcone chemicals, could induce the apoptosis of cancer cells. HeLa cells were treated with NPs and the cell viability was evaluated using WST-1 assay. Protein expression of Ki-67 was measured using immunocytochemistry. In addition, the apoptotic effect of NPs was determined using TUNEL assay. To investigate the apoptosis signaling pathways, reverse transcription quantitative PCR was performed and lipid accumulation was observed via holotomographic microscopy. The IC50 value of the NPs was 4.172 µM in HeLa cells. Furthermore, 10 µM NPs significantly inhibited the cell proliferation and stimulated the apoptosis of HeLa cells. In addition, apoptosis and mitochondrial dysfunction were induced by the NPs through lipid accumulation in HeLa cells, leading to apoptotic signaling cascades. Taken together, the results from the present study demonstrated that the NPs developed promoted apoptosis though efficient lipid accumulation in HeLa cells, suggesting that they may provide a novel way to improve the efficacy of CVC anticancer treatment.

A network pharmacology approach to explore the potential role of Panax ginseng on exercise performance.

PURPOSE: As Panax ginseng C. A. Meyer (ginseng) exhibits various physiological activities and is associated with exercise, we investigated the potential active components of ginseng and related target genes through network pharmacological analysis. Additionally, we analyzed the association between ginseng-related genes, such as the G-protein-coupled receptors (GPCRs), and improved exercise capacity. METHODS: Active compounds in ginseng and the related target genes were searched in the Traditional Chinese Medicine Database and Analysis Platform (TCMSP). Gene ontology functional analysis was performed to identify biological processes related to the collected genes, and a compound-target network was visualized using Cytoscape 3.7.2. RESULTS: A total of 21 ginseng active compounds were detected, and 110 targets regulated by 17 active substances were identified. We found that the active compound protein was involved in the biological process of adrenergic receptor activity in 80%, G-protein-coupled neurotransmitter in 10%, and leucocyte adhesion to arteries in 10%. Additionally, the biological response centered on adrenergic receptor activity showed a close relationship with G protein through the beta-1 adrenergic receptor gene reactivity. CONCLUSION: According to bioavailability analysis, ginseng comprises 21 active compounds. Furthermore, we investigated the ginseng-stimulated gene activation using ontology analysis. GPCR, a gene upregulated by ginseng, is positively correlated to exercise. Therefore, if a study on this factor is conducted, it will provide useful basic data for improving exercise performance and health.

Feasibility of TSPO-Specific Positron Emission Tomography Radiotracer for Evaluating Paracetamol-Induced Liver Injury.

Macrophages are activated during the early phase of paracetamol-induced liver injury (PLI). [18F]GE180 is a radiolabeled ligand that recognizes the macrophage translocator protein (TSPO). In this study, we evaluated the feasibility of a TSPO-specific radiotracer in a rat model of PLI. A rat model of liver injury was induced by intraperitoneal administration of paracetamol. [18F]GE180 positron emission tomography (PET) images were obtained after 24 h. The maximal and mean standardized uptake values (SUVmax and SUVav) of the liver and serum biomarker levels were examined. The TSPO expression level was examined using real-time polymerase chain reaction and Western blot analysis. [18F]GE180 hepatic uptake in the PLI group was significantly higher than that in the control group (SUVmax p = 0.001; SUVav p = 0.005). Both mRNA and protein TSPO expression levels were higher in the PLI group. The mRNA expression level of TSPO was significantly correlated with [18F]GE180 hepatic uptake in both groups (SUVmax p = 0.019; SUVav p = 0.007). [18F]GE180 hepatic uptake in the PLI group showed a significant positive correlation with ALT24 and ALT48 (ALT24 p = 0.016; ALT48p = 0.002). [18F]GE180 enabled visualization of PLI through TSPO overexpression. Our results support the potential utility of hepatic uptake by TSPO-PET as a non-invasive imaging biomarker for the early phase of PLI.

18F-FET PET/CT as a Diagnostic Tool for Brain Abscess.

ABSTRACT: A 49-year-old man presented with sudden right-sided weakness and seizure. Brain MRI identified a lobulated mass with diffusion restriction and irregular wall enhancement in the left parietal lobe. 18F-FET (O-(2-[18F]fluoroethyl)-l-tyrosine) PET/CT was performed, which identified a cystic mass in the left parietal lobe accompanied by FET uptake. Compartmentalized uptake was also confirmed throughout the left parietal lobe. Considering the relatively low target-to-background ratio and uptake observed in the entire left parietal lobe, the lesion was more likely to be a brain abscess than a tumor. The pathologic diagnosis after mass removal was acute and chronic inflammation with abscess.

TSPO Expression Modulatory Effect of Acetylcholinesterase Inhibitor in the Ischemic Stroke Rat Model.

We performed in vivo PET imaging with 3-[18F]F-CP118,954 (1) for acetylcholinesterase (AChE) and [18F]fluoromethyl-PBR28-d2 (2) for translocator protein 18-kDa (TSPO) to investigate the inflammatory brain response after stroke. Imaging studies were performed in the middle cerebral artery occlusion (MCAO) Sprague-Dawley rat model for a period of three weeks. The percentage injected dose per tissue weight (%ID/g) of striatum of 1, and cortex of 2 were obtained, respectively. To trace the sequential inflammatory responses, AChE imaging of 1 was done on post-MCAO day 2, after giving cold PK-11195 for 1 day, and TSPO imaging of 2 was carried out on post-MCAO day 11, after giving donepezil for 10 days. AChE activity in the MCAO-lesioned side were significantly higher than that of the contralateral side on day one, and TSPO activity was highest on day 11. TSPO inhibitor, PK-11195 did not affect AChE activity on day two, while AChE inhibitor, donepezil significantly lowered TSPO binding on day 12. Our study demonstrates that AChE level is elevated in the early course of brain ischemia as a trigger for the inflammatory response, and TSPO level is elevated persistently throughout the post-ischemic injury in the brain. Also, the AChE inhibitor may be able to inhibit or delay neurotoxic inflammatory responses and serve as a beneficial treatment option.

Tissue pharmacokinetics of DHP107, a novel lipid-based oral formulation of paclitaxel, in mice and patients by positron emission tomography.

DHP107 is a newly developed lipid-based oral formulation of paclitaxel. We evaluated the in vivo tissue pharmacokinetics (PKs) of DHP107 in mice and patients using positron emission tomography (PET). Radioisotope-labeled [3 H]DHP107 and [18 F]DHP107 for oral administration were formulated in the same manner as the manufacturing process of DHP107. In vivo tissue PK were assessed in healthy ICR mice and breast cancer xenografted SCID mice. Two patients with metastatic breast cancer were clinically evaluated for absorption at the target lesion after internal absorbed dose estimation. Whole-body PET/computed tomography data were acquired in healthy and xenografted mice and in patients up to 10-24 h after administration. Tissue [18 F]DHP107 signals were plotted against time and PK parameters were determined. The amounts of radioactivity in various organs and excreta were determined using a beta-counter and are expressed as the percentage of injected dose (ID). Oral [18 F]DHP107 was well-absorbed and reached the target lesion in mice and patients with breast cancer. Significant amounts of radioactivity were found in the stomach, intestine, and liver after oral administration of [3 H]- and [18 F]DHP107 in healthy mice. The [18 F]DHP107 reached a peak distribution of 0.7-0.8%ID in the tumor at 5.6-7.3 h in the xenograft model. The [18 F]DHP107 distribution in patients with metastatic breast cancer was the highest at 3-4 h postadministration. Systemic exposures after administration of a DHP107 therapeutic dose were comparable with those in previous studies. PET using radioisotope-labeled drug candidates is useful for drug development and can provide valuable information that can complement plasma PK data, particularly in early phase clinical trials.

Lymphoscintigraphic Findings as Indicators of Lymphaticovenous Anastomosis Outcome in Patients With Extremity Lymphedema: A Retrospective Cohort Study.

PURPOSE: This study was performed to evaluate the usefulness of lymphoscintigraphy in predicting the surgical outcomes of lymphaticovenous anastomosis (LVA) in a patient with extremity lymphedema. PATIENTS AND METHODS: We retrospectively evaluated 133 patients with extremity lymphedema who underwent lymphoscintigraphy followed by LVA surgery from February 2018 to March 2020. Lymphoscintigraphic findings were evaluated on the following parameters: the extent of dermal backflow (small/large), lymphatic flow patterns (trunk flow pattern/proximal-restricted pattern/distal-restricted pattern), visualization of lymph nodes, and collateral lymphatic vessels. The mean circumferential difference change before and after surgery, circumferential reduction (CR) rate (%), was used as the clinical outcome variables. RESULTS: A decrease in circumference was observed in 93 (69.9%) of 133 patients after LVA. The extent of dermal backflow and lymphatic flow patterns was significantly correlated with improved clinical outcomes after LVA. The large extent of the dermal backflow group showed a more significant CR rate than the small extent (19.27% vs 1.24%, P = 0.005). The TP group showed the most significantly decreased CR rate to 21.46%, and the proximal-restricted pattern and distal-restricted pattern groups were -2.49% and -5.33%, respectively (P < 0.001). Multivariate analysis revealed that dermal backflow and lymphatic flow patterns were independent predictors of therapeutic outcome (P < 0.001). CONCLUSIONS: Our study demonstrates that pretreatment lymphoscintigraphy may help predict the therapeutic effect of LVA in patients with extremity lymphedema. Furthermore, dermal backflow and lymphatic flow patterns are independent predictors of CR rate after LVA surgery for extremity lymphedema.

Radioactive Iodine Treatment for Children and Young Adults with Thyroid Cancer in South Korea: A Population-based Study.

PURPOSE: This study investigated radioactive iodine treatment (RAIT) patterns and the secondary cancer incidence among children and young adults receiving RAIT after thyroidectomy for thyroid cancer. METHODS: This population-based cohort study used the Health Insurance Review and Assessment database of South Korea to identify a total of 18 617 children and young adults (0-29 years) who underwent thyroidectomy for thyroid cancer between 2008 and 2018. We recorded age at surgery, sex, the interval from surgery to RAIT, the doses of RAI, the number of RAIT sessions, and secondary cancer incidence. RESULTS: A total of 9548 (51.3%) children and young adults underwent 1 or more RAIT sessions. The initial dose of RAIT was 4.35 ±â€…2.19 GBq. The overall RAIT frequency fell from 60.9% to 38.5%, and the frequency of high-dose RAIT (>3.7 GBq) fell from 64.2% to 36.5% during the observational period. A total of 124 cases of secondary cancer developed during 120 474 person-years of follow-up; 43 (0.5%) in the surgery cohort and 81 (0.8%) in the RAIT cohort. Thus, the RAIT cohort was at an increased risk of secondary cancer (adjusted hazard ratio 1.52 [95% confidence interval 1.03-2.24], P = 0.035). CONCLUSION: The proportion of children and young adults receiving RAIT, and the RAI dose, fell significantly over the observational period. RAIT was associated with secondary cancers. This is of major concern in the context of child and young adult thyroid cancer survivors.