Auger emitter in combination with Olaparib suppresses tumor growth via promoting antitumor immune responses in pancreatic cancer.

The present study aimed to clarify the hypothesis that auger emitter 125I particles in combination with PARP inhibitor Olaparib could inhibit pancreatic cancer progression by promoting antitumor immune response. Pancreatic cancer cell line (Panc02) and mice subcutaneously inoculated with Panc02 cells were employed for the in vitro and in vivo experiments, respectively, followed by 125I and Olaparib administrations. The apoptosis and CRT exposure of Panc02 cells were detected using flow cytometry assay. QRT-PCR, immunofluorescence, immunohistochemical analysis, and western blot were employed to examine mRNA and protein expression. Experimental results showed that 125I combined with Olaparib induced immunogenic cell death and affected antigen presentation in pancreatic cancer. 125I in combination with Olaparib influenced T cells and dendritic cells by up-regulating CD4, CD8, CD69, Caspase3, CD86, granzyme B, CD80, and type I interferon (IFN)-γ and down-regulating Ki67 in vivo. The combination also activated the cyclic GMP-AMP synthase stimulator of IFN genes (Sting) pathway in Panc02 cells. Moreover, Sting knockdown alleviated the effect of the combination of 125I and Olaparib on pancreatic cancer progression. In summary, 125I in combination with Olaparib inhibited pancreatic cancer progression through promoting antitumor immune responses, which may provide a potential treatment for pancreatic cancer.

CT-guided radioactive 125I seeds brachytherapy for lung oligometastases from colorectal cancer: initial results.

OBJECTIVES: To evaluate the safety and effectiveness of computed tomography (CT)-guided radioactive 125I seeds brachytherapy (RISB) for lung oligometastases (LO) from colorectal cancer (CRC). METHODS: Data for 144 LOs from 70 CRC patients who underwent CT-guided RISB were retrospectively analyzed. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints were technical success, local control rate (LCR), and complications. Kaplan-Meier method was used for survival analysis. Cox model was used to identify the independent predictors of poor prognosis. RESULTS: The RISB procedures were successfully performed in all patients, and the success rate was 100%. The median follow-up was 27.8 months. The median PFS was 10.0 months (95% CI: 8.9-11.1) and the 1- and 2-year PFS rates were 32.9% and 5.9%, respectively. On multivariate analysis, serum carcinoembryonic antigen (CEA) ≤ 15 ng/ml (P = 0.048), middle-high differentiated pathological classification (P = 0.015), primary TNM stages I-III (P = 0.001), LO number ≤ 2 (P < 0.001) and cumulative gross tumor volume (GTV) ≤ 40 cm3 (P < 0.001) showed superior PFS. The median OS was 30.8 months (95% CI: 27.1-34.4) and the 1-, 2-, and 3-year OS rates were 95.7%, 67.4%, and 42.5%, respectively. On multivariate analysis, serum CEA ≤ 15 ng/ml (P = 0.004), middle-high differentiated pathological classification (P < 0.001), primary TNM stages I-III (P < 0.001), LO number ≤ 2 (P < 0.001), cumulative GTV ≤ 40 cm3 (P < 0.001) and system treatments combined with chemotherapy and target therapy (P < 0.001) showed superior OS. The LCR for 3, 6, and 12 months was 97.9%, 91.0%, and 83.6%, respectively. There were 4 cases of pneumothorax at 5.7% that required drainage. CONCLUSIONS: RISB for LO from CRC is safe and effective, and serum CEA, TNM stage, LO number, cumulative GTV, and system treatments should be emphasized for long OS.

Preparation of Radiolabeled Zolbetuximab Targeting CLDN18.2 and Its Preliminary Evaluation for Potential Clinical Applications.

Claudin18.2 (CLDN18.2), due to its high expression in various gastric cancer tissues, is considered an optimal target for antitumor drug molecules. In this study, we obtained the labeled compounds of [125I]I-zolbetuximab using the Iodogen method. Under the optimum labeling conditions, the molar activity of [125I]I-zolbetuximab was 1.75 × 102 GBq/µmol, and the labeling efficiency was more than 99%. The labeled compounds exhibited excellent in vitro stability in both phosphate buffer saline (PBS, pH = 7.4) and fetal bovine serum systems (FBS) (radiochemical purity >90% at 72 h). The uptake percentage of [125I]I-zolbetuximab in MKN45-CLDN18.2 cells is 24.69 ± 0.84% after 6 h. The saturation binding assay and specificity assay further demonstrated the high specificity of [125I]I-zolbetuximab for CLDN18.2. The long retention at the tumor site and rapid metabolic clearance at other organ sites of [125I]I-zolbetuximab were observed in small-animal SPECT-CT imaging. The same trend was also observed in the biodistribution study. Due to the excellent targeting ability of zolbetuximab for CLDN18.2, [125I]I-zolbetuximab exhibits strong specific binding and retention with cells and tumors highly expressing CLDN18.2. However, the balance between mAb's longer cycle time in vivo and targeting binding and retention ability should be intensively considered for using this kind of radiopharmaceutical in the diagnosis and treatment of CLDN18.2-positive gastric cancer.

Intraoperative implantation of 125I seeds improves prognosis in refractory stage IIIB cervical cancer: a case report and literature review.

BACKGROUND: Concurrent chemoradiation is the standard treatment for advanced cervical cancer. However some patients still have a poor prognosis, and currently, there is no effective treatment for recurrence. In recent years, 125I seed implantation therapy has emerged as a treatment for advanced malignant tumors including surgically unresectable tumors, residual tumors after surgical resection, and metastatic tumors. However, the use of 125I seeds implantation in primary advanced cervical cancer has not been reported. In this study, we present a case of stage IIIB cervical cancer in a patient who had poor response to radiotherapy and chemotherapy. Subsequently, a radical hysterectomy was performed, and 125I radioactive seeds were successfully implanted during the surgery. This effectively controlled the lesions that were resistant to radiotherapy and had the potential to improve the prognosis. CASE PRESENTATION: A 56-year-old woman was diagnosed with stage IIIB (FIGO 2009) IIIC1r (FIGO 2018) squamous carcinoma of the cervix. After receiving 4 cycles of platinum-based chemotherapy and 30 rounds of radiotherapy, she underwent a radical hysterectomy. The localized cervical lesions were reduced, but there was no reduction in the size of the enlarged pelvic lymph nodes. Therefore, 125I seed implantation was performed under direct surgical vision for the right paracervical lesion and the enlarged pelvic lymph nodes on the right side. During the 18-month follow-up period, the enlarged lymph nodes subsided without any signs of recurrence or metastasis. CONCLUSION: Intraoperative implantation of 125I seeds in lesions that are difficult to control with radiotherapy or in sites at high risk of recurrence is a feasible and effective treatment option for patients with advanced squamous cervical cancer, and it may contribute to improved survival.

Radioiodinated Tau Imaging Agent III Molecular Modeling, Synthesis, and Evaluation of a New Tau Imaging Agent, [125I]ISAS in Post-Mortem Human Alzheimer's Disease Brain.

Using a molecular modeling approach for Tau-binding sites, we modified our previously reported imaging agent, [125I]INFT, for the potential improvement of binding properties to Tau in an Alzheimer's disease (AD) brain. Two new derivatives, namely [125I]ISAS and [125I]NIPZ, were designed, where binding energies at site 1 of Tau were -7.4 and -6.0 kcal/mole, respectively, compared to [125I]INFT (-7.6 kcal/mole). The radiosynthesis of [125I]ISAS and [125I]NIPZ was carried out by using iodine-125 and purified chromatographically to achieve >90% purity. In vitro binding affinities (IC50) for Tau were as follows: INFT = 7.3 × 10-8 M; ISAS = 4.7 × 10-8 M; NIPZ > 10-6 M. The binding of [125I]ISAS to gray matter (GM) correlated with the presence of Tau in the AD brain, confirmed by anti-Tau immunohistochemistry. [125I]NIPZ did not bind to Tau, with similar levels of binding observed in GM and white matter (WM). Four radiotracers were compared and the rank order of binding to Tau was found to be [125I]IPPI > [125I]INFT > [125I]ISAS >>> [125I]NIPZ with GM/WM ratios of [125I]IPPI = 7.74 > [125I]INFT = 4.86 > [125I]ISAS = 3.62 >> [125I]NIPZ = 1.24. The predictive value of Chimera-AutoDock for structurally related compounds binding to the Tau binding sites (measured as binding energy) was good. A binding energy of less than -7 kcal/mole is necessary and less than -8 kcal/mole will be more suitable for developing imaging agents.

Circular RNA circEYA3 promotes the radiation resistance of hepatocellular carcinoma via the IGF2BP2/DTX3L axis.

BACKGROUND: Hepatocellular carcinoma (HCC) has a high incidence and mortality rate despite various treatment options, including 125I seed implantation. However, recurrence and radiation resistance remain challenging issues. Hsa_circ_0007895 (circEYA3)-derived from exons 2-6 of EYA3-facilitates the proliferation and progression of pancreatic ductal adenocarcinoma. However, the role of circEYA3 in HCC 125I radiation resistance remains unclear. Thus, we aimed to investigate the functions and underlying molecular mechanisms of circEYA3 in HCC under 125I and X-ray irradiation conditions. METHODS: CircEYA3 was identified by RNA-seq in patients with HCC before and after 125I seed implantation treatment, followed by fluorescence in situ hybridization and RNase R assays. The radiosensitivity of HCC cell lines irradiated with 125I seeds or external irradiation were evaluated using the Cell Counting Kit 8, flow cytometry, γH2A.X immunofluorescence and comet assays. RNA pull-down and RNA immunoprecipitation assays were performed to explore the interactions between circEYA3 and IGF2BP2. DTX3L mRNA was identified by RNA-seq in PLC/PRF/5 cells with overexpressed circEYA3. The corresponding in vitro results were verified using a mouse xenograft model. RESULTS: CircEYA3 decreased the radiosensitivity of HCC cells both in vitro and in vivo. Notably, using a circRNA pulldown assay and RNA-binding protein immunoprecipitation, we identified IGF2BP2 as a novel and robust interacting protein of circEYA3. Mechanistically, circEYA3 binds to IGF2BP2 and enhances its ability to stabilize DTX3L mRNA, thereby specifically alleviating radiation-induced DNA damage in HCC cells. CONCLUSIONS: Our findings demonstrate that circEYA3 increases the radioresistance of HCC to 125I seeds and external irradiation via the IGF2BP2/DTX3L axis. Thus, circEYA3 might be a predictive indicator and intervention option for 125I brachytherapy or external radiotherapy in HCC.

Biliary drainage combined with simultaneous 125I seed strand brachytherapy for the treatment of hilar cholangiocarcinoma.

BACKGROUND: To evaluate the clinical efficacy of percutaneous biliary drainage (PBD) combined with 125I seed strand brachytherapy (ISSB) for the treatment of hilar cholangiocarcinoma (HCCA). METHODS: The clinical data of 64 patients with HCCA (median age 62.5, male 29, female 35) treated in our department from April 2017 to April 2021 were retrospectively analyzed. Thirty-four patients in the experimental group (EG) were treated with PBD combined with ISSB, while 30 patients in the control group (CG) were treated with PBD alone. The primary study endpoints were technical success, clinical success and the 2-month local tumor control (LTC) rate. Secondary endpoints were early/late complications, median progression-free survival (mPFS) and overall survival (mOS). RESULTS: The technical and clinical success in the EG and CG showed no significant differences (100 vs. 100%, 94.1 vs. 93.3%, P > 0.05). Both early and late complications showed no significant differences between the two groups (P > 0.05). The 2-month LTC rates were significantly better in the EG versus the CG (94.1% vs. 26.7%, 157.7 ± 115.3 vs. 478.1 ± 235.3 U/ml), respectively (P < 0.05). The mPFS and mOS were 4.3 (95% CI 3.9-4.7) months and 2.8 (95% CI 2.5-3.1) months and 13.5 (95% CI 10.7-16.3) months and 8.8 (95% CI 7.8-9.8) months, respectively, with significant differences (P < 0.05). CONCLUSION: PBD combined with ISSB is a safe and effective treatment for HCCA that can inhibit local tumors and prolong PFS and OS.

Abnormal [18 F]NIFENE binding in transgenic 5xFAD mouse model of Alzheimer's disease: In vivo PET/CT imaging studies of α4ß2* nicotinic acetylcholinergic receptors and in vitro correlations with Aß plaques.

Since cholinergic dysfunction has been implicated in Alzheimer's disease (AD), the effects of Aß plaques on nicotinic acetylcholine receptors (nAChRs) α4ß2* subtype were studied using the transgenic 5xFAD mouse model of AD. Using the PET radiotracer [18 F]nifene for α4ß2* nAChRs, in vitro autoradiography and in vivo PET/CT studies in 5xFAD mice were carried out and compared with wild-type (C57BL/6) mice. Ratios of [18 F]nifene binding in brain regions versus cerebellum (CB) in 5xFAD mice brains were for thalamus (TH) = 17, hippocampus-subiculum = 7, frontal cortex (FC) = 5.5, and striatum = 4.7. [125 I]IBETA and immunohistochemistry (IHC) in 5xFAD brain slices confirmed Aß plaques. Nicotine and acetylcholine displaced [18 F]nifene in 5xFAD mice (IC50 nicotine = 31-73 nM; ACh = 38-83 nM) and C57BL/6 (IC50 nicotine = 16-18 nM; ACh = 34-55 nM). Average [18 F]nifene SUVR (CB as reference) in 5xFAD mice was significantly higher in FC = 3.04 compared to C57BL/6 mice FC = 1.92 (p = .001), whereas TH difference between 5xFAD mice (SUVR = 2.58) and C57BL/6 mice (SUVR = 2.38) was not significant. Nicotine-induced dissociation half life (t1/2 ) of [18 F]nifene for TH were 37 min for 5xFAD mice and 26 min for C57BL/6 mice. Dissociation half life  for FC in C57BL/6 mice was 77 min , while no dissociation of [18 F]nifene occurred in the medial prefrontal cortex (mFC) of 5xFAD mice. Coregistration of [18 F]nifene PET with MR suggested that the mPFC, and anterior cingulate (AC) regions exhibited high uptake in 5xFAD mice compared to C57BL/6 mice. Ex vivo [18 F]nifene and in vitro [125 I]IBETA Aß plaque autoradiography after in vivo PET/CT scan of 5xFAD mouse brain were moderately correlated (r2 = 0.68). In conclusion, 5xFAD mice showed increased non-displaceable [18 F]nifene binding in mPFC.

125I-labeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (125I-OI5V) imaging visualized augmented sigma-1 receptor expression according to the severity of myocardial ischemia.

BACKGROUND: We aimed to explore how the severity of myocardial ischemia affects myocardial sigma-1 receptor (Sig-1R) expression using 125I-labeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (125I-OI5V) imaging. METHODS AND RESULTS: The left coronary artery was occluded for 30, 20, and 10 minute, to vary the severity of myocardial ischemia, followed by reperfusion. Dual-tracer autoradiography of the left ventricular short-axis slices was performed 3 and 7 days after reperfusion. 125I-OI5V was injected 30 minute before sacrifice and the area at risk (AAR) was evaluated by 99mTc-MIBI. Intense 125I-OI5V uptake was observed in the AAR and was significantly increased with increasing ischemia duration. To evaluate salvaged and nonsalvaged areas (preserved and decreased perfusion areas), triple-tracer autoradiography was performed 3 days after reperfusion. After dual-tracer autoradiography, 201Tl was injected 20 minute post 125I-OI5V injection. On triple-tracer autoradiography, the AAR/normally perfused area 125I-OI5V uptake ratio was positively correlated with the nonsalvaged area/whole left ventricular (LV) area ratio (P < .05). The AAR/normally perfused area 125I-OI5V uptake ratio was negatively correlated with the 201Tl uptake ratio of the AAR to normally perfused areas (P < .05). The comparison of the immunostaining distribution of 125I-OI5V and the macrophage marker CD68 revealed that 125I-OI5V was present mainly in, and immediately adjacent to the macrophage infiltration area. CONCLUSIONS: Significant 125I-OI5V uptake in the AAR depends on the duration of ischemia and reduced 201Tl uptake; furthermore, 125I-OI5V was found in and around the macrophage infiltrate area. These results indicate that iodine-labeled OI5V is a promising tool for visualizing Sig-1R expression according to the ischemic burden.

Biliary self-expandable metallic stent combined with iodine-125 seeds in the treatment of malignant biliary obstruction (Bismuth type I or II).

BACKGROUND: The purpose of this research was to evaluate the safety and efficacy of a self-expandable metallic stent (SEMS) combined with iodine-125 (125I) seeds in the treatment of Bismuth type I or II malignant biliary obstruction (MBO). METHODS: The clinical data of 74 cases of MBO treated with percutaneous SEMS combined with 125I seeds (combination group) and 81 cases of MBO treated with SEMS implantation alone (control group) in our hospital from January 2015 to December 2019 were retrospectively analyzed. The short-term and long-term efficacy of the two groups were compared. Multivariate Cox regression analysis was used to analyze the factors affecting the surgical efficacy and survival rate. RESULTS: The liver blood test results of both groups improved at one week and one month post-stent insertion. No significant difference was established in the short-term efficacy or complications between the two groups (P = NS). Improved stent patency was observed in the combined group, 9.01 ± 4.38 months versus 6.79 ± 3.13 months, respectively (P < 0.001). Improved survival was also noted in the combined group 12.08 ± 5.38 months and 9.10 ± 4.16 months, respectively (P < 0.001). Univariate and multivariate analyses showed that the type of biliary stent and liver metastasis were independent factors affecting survival. CONCLUSION: The implementation of SEMS combined with 125I seeds resulted in significantly longer stent patency and survival times than that of SEMS implantation alone, which is thus worthy of clinical promotion and application.

Prognostic analysis of percutaneous vertebroplasty (PVP) combined with 125I implantation on lumbosacral vertebral osteoblastic metastases.

OBJECTIVE: Lumbosacral vertebral osteoblastic metastasis is treated with percutaneous vertebroplasty (PVP) combined with 125I seed implantation and PVP alone. Compared to PVP alone, we evaluated the effects of combination therapy with PVP and 125I seed implantation on pain, physical condition, and survival and evaluated the clinical value of PVP combined with 125I particle implantation. METHODS: We retrospectively analyzed 62 patients with lumbosacral vertebral osseous metastases treated at our hospital between 2016 and 2019. All the patients met the inclusion criteria for 125I implantation, and they were randomly divided into a combined treatment group and a pure PVP surgery group. The visual analog pain scale (VAS), Karnofsky Performance Status (KPS), and survival time were recorded at different time points, including preoperative, postoperative 1 day, 1 month, 3 months, 6 months, 12 months, and 36 months in each group. The variation in clinical indicators and differences between the groups were analyzed using SPSS version 20.0. Correlations between different variables were analyzed using the nonparametric Spearman's rank test. The Kaplan-Meier method was used to estimate the relationship between survival time and KPS score, VAS score, or primary tumor progression, and survival differences were analyzed using the log-rank test. Multivariate analyses were performed using a stepwise Cox proportional hazards model to identify independent prognostic factors. RESULTS: Compared to the PVP treatment group, the pain level in the combined treatment group was significantly reduced (P = 0.000), and the patient's physical condition in the combination treatment group significantly improved. Kaplan-Meier analysis showed that the survival rate of the PVP group was significantly lower than that of the combination group (P = 0.038). We also found that the median survival of patients in both groups significantly increased with an increase in the KPS score (14 months vs. 33 months) (P = 0.020). Patients with more than three transfer sections had significantly lower survival rates than those with one or two segments of the section (P = 0.001). Further, Cox regression analysis showed that age (P = 0.002), the spinal segment for spinal metastasis (P = 0.000), and primary tumor growth rate (P = 0.005) were independent factors that affected the long-term survival of patients with lumbosacral vertebral osseous metastases. CONCLUSIONS: PVP combined 125I seeds implantation surgery demonstrated superior effectiveness compared to PVP surgery alone in treating lumbosacral vertebral osseous metastases, which had feasibility in the clinical operation. Preoperative KPS score, spine transfer section, and primary tumor growth rate were closely related to the survival of patients with lumbosacral vertebral osteoblastic metastasis. Age, spinal segment for spinal metastasis, and primary tumor growth can serve as prognostic indicators and guide clinical treatment.

Comparison of Monoamine Oxidase-A, Aß Plaques, Tau, and Translocator Protein Levels in Postmortem Human Alzheimer's Disease Brain.

Increased monoamine oxidase-A (MAO-A) activity in Alzheimer's disease (AD) may be detrimental to the point of neurodegeneration. To assess MAO-A activity in AD, we compared four biomarkers, Aß plaques, tau, translocator protein (TSPO), and MAO-A in postmortem AD. Radiotracers were [18F]FAZIN3 for MAO-A, [18F]flotaza and [125I]IBETA for Aß plaques, [124/125I]IPPI for tau, and [18F]FEPPA for TSPO imaging. Brain sections of the anterior cingulate (AC; gray matter GM) and corpus callosum (CC; white matter WM) from cognitively normal control (CN, n = 6) and AD (n = 6) subjects were imaged using autoradiography and immunostaining. Using competition with clorgyline and (R)-deprenyl, the binding of [18F]FAZIN3 was confirmed to be selective to MAO-A levels in the AD brain sections. Increases in MAO-A, Aß plaque, tau, and TSPO activity were found in the AD brains compared to the control brains. The [18F]FAZIN3 ratio in AD GM versus CN GM was 2.80, suggesting a 180% increase in MAO-A activity. Using GM-to-WM ratios of AD versus CN, a >50% increase in MAO-A activity was observed (AD/CN = 1.58). Linear positive correlations of [18F]FAZIN3 with [18F]flotaza, [125I]IBETA, and [125I]IPPI were measured and suggested an increase in MAO-A activity with increases in Aß plaques and tau activity. Our results support the finding that MAO-A activity is elevated in the anterior cingulate cortex in AD and thus may provide a new biomarker for AD in this brain region.

[125I]INFT: Synthesis and Evaluation of a New Imaging Agent for Tau Protein in Post-Mortem Human Alzheimer's Disease Brain.

Aggregation of Tau protein into paired helical filaments causing neurofibrillary tangles (NFT) is a neuropathological feature in Alzheimer's disease (AD). This study aimed to develop and evaluate the effectiveness of a novel radioiodinated tracer, 4-[125I]iodo-3-(1H-pyrrolo[2,3-c]pyridine-1-yl)pyridine ([125I]INFT), for binding to Tau protein in postmortem human AD brain. Radiosynthesis of [125I]INFT was carried out using electrophilic destannylation by iodine-125 and purified chromatographically. Computational modeling of INFT binding on Tau fibril was compared with IPPI. In vitro, autoradiography studies were conducted with [125I]INFT for Tau in AD and cognitively normal (CN) brains. [125I]INFT was produced in >95% purity. Molecular modeling of INFT revealed comparable binding energies to IPPI at site-1 of the Tau fibril with an affinity of IC50 = 7.3 × 10-8 M. Binding of [125I]INFT correlated with the presence of Tau in the AD brain, confirmed by anti-Tau immunohistochemistry. The ratio of average grey matter (GM) [125I]INFT in AD versus CN was found to be 5.9, and AD GM/white matter (WM) = 2.5. Specifically bound [125I]INFT to Tau in AD brains was displaced by IPPI (>90%). Monoamine oxidase inhibitor deprenyl had no effect and clorgyline had little effect on [125I]INFT binding. [125I]INFT is a less lipophilic imaging agent for Tau in AD.

Synthesis and Evaluation of Compound Targeting α7 and ß2 Subunits in Nicotinic Acetylcholinergic Receptor.

Nicotinic acetylcholine receptors (nAChRs) are involved in various central nervous system functions and have also been implicated in several neurodegenerative disorders. The heteromeric α4ß2* and homomeric α7 are two major nAChR subtypes which have been studied in the brain using positron emission tomography (PET). Our comparative autoradiographic studies of the two receptor types in the mouse and rat brains show major differences in the thalamus (α4ß2* >> α7), hippocampus (α7 >> α4ß2*), and subiculum (α4ß2* >> α7). A relatively newer heteromeric α7ß2 nAChR subtype has been identified in the brain which may have a greater role in neurodegeneration. We report the development of KS7 (3-(2-(S)-azetidinylmethoxy)-5-(1,4-diaza-bicyclo[3.2.2]nonane)pyridine) which incorporates structural features of Nifzetidine (high affinity for α4ß2* nAChR) and ASEM (high affinity for α7 nAChR) in an effort to target α7 and ß2 subunits in α7ß2 nAChR. KS7 exhibited higher affinities (IC50 = 50 to 172 nM) for [3H]cytisine radiolabeled sites and weaker affinities (IC50 = 10 µM) for [125I]-α-bungarotoxin radiolabeled rat brain sites in several brain regions. The weaker affinity of KS7 to α7 nAChR may suggest lack of binding at the α7 subunit of α7ß2 nAChR. A radiolabeled derivative of KS7 may be required to identify any specific binding to brain regions suggested to contain α7ß2 nAChR.

Effect of neoadjuvant iodine-125 brachytherapy upon resection of glioma.

BACKGROUND: A more extensive surgical resection of glioma contributes to improved overall survival (OS) and progression-free survival (PFS). However, some patients miss the chance of surgical resection when the tumor involves critical structures. PURPOSE: The present study aimed to assess the feasibility of neoadjuvant 125I brachytherapy followed by total gross resection for initially inoperable glioma. METHODS: Six patients diagnosed with inoperable glioma due to invasion of eloquent areas, bihemispheric diffusion, or large tumor volume received 125I brachytherapy. Surgical resection was performed when the tumor shrank, allowing a safe resection, assessed by the neurosurgeons. Patients were followed up after surgery. RESULTS: Shrinkage of the tumor after adjuvant 125I brachytherapy enabled a total gross resection of all six patients. Four patients were still alive at the last follow-up, with the longest survival time of more than 50 months, two of which returned to everyday life with a KPS of 100. Another two patients had neurological injuries with KPSs of 80 and 50, respectively. One patient with grade II glioma died 34 months, and another with grade IV glioma died 40 months after the combined therapy. CONCLUSIONS: In the present study, the results demonstrated that 125I brachytherapy enabled a complete resection of patients with initially unresectable gliomas. 125I brachytherapy may offer a proper neoadjuvant therapy method for glioma.

Preliminary application of brachytherapy with double-strand 125I seeds and biliary drainage for malignant obstructive jaundice.

AIM: To evaluate the efficacy and safety of brachytherapy with double-strand 125I seeds and biliary drainage for malignant obstructive jaundice. METHODS AND MATERIALS: 42 patients with obstructive jaundice because of extrahepatic cholangiocarcinoma were enrolled. 22 patients (group A) received a biliary stent with common drainage tube implantation, and 20 patients (group B) received a biliary stent with double-strand 125I seeds radiotherapy drainage tube placement. The length, location and pathological stage of biliary stricture were recorded in the two groups. Total bilirubin (TBIL), direct bilirubin (DBIL), IgA, IgG, IgM, alanine aminotransferase and white blood cell (WBC) count were measured before and after percutaneous transhepatic cholangial drainage (PTCD). Tumor diameter was measured before and three months after PTCD, and the difference were calculated. Stent patency time, survival time, and complications were recorded. RESULTS: There was no significant difference in the length, location and pathological stage of biliary stenosis between the two groups. There was no significant difference in TBIL, DBIL, IgA, IgG, IgM, alanine aminotransferase and WBC count between the two groups before or after PTCD (P > 0.05). Three months after PTCD, tumors growth in group A and tumors shrinkage in group B. The difference in tumor size between the two groups before and after PTCD was statistically significant (P < 0.05). The average stent patency times in groups A and B were 3.55 ± 0.76 months and 8.76 ± 1.85 months, respectively (P < 0.05). The average survival times in groups A and B were 133.5 ± 27.8 days and 252.5 ± 114.5 days, respectively (P < 0.05). There was no statistically significant difference in the incidence of complications between the two groups (P > 0.05). CONCLUSION: Double-strand 125I seeds radiotherapy biliary drainage tubes can safely and effectively control tumors, prolong the patency of biliary stents, and prolong patient survival.

Application value of the treatment of breast cancer bone metastases with radioactive seed 125I implantation under CT-guidance.

BACKGROUND: To investigate the application value of the treatment of breast cancer bone metastases with radioactive seed 125I implantation under CT-guidance. METHODS: A total of 90 patients with breast cancer admitted to our hospital from January 2017 to January 2018 were selected as the research objects and were divided into control group and experimental group according to random grouping, with 45 cases in each group. Conventional treatment was used in the control group, while the treatment of radioactive seed 125I implantation under CT-guidance was used in the experimental group. The clinical efficacy, pain intensity and levels of carcinoembryonic antigen (CEA), carcinoembryonic antigen 153 (CA153), carbohydrate antigen (CA125) in the two groups were compared. RESULTS: As for the pain intensity, it was evidently lower in the experimental group after treatment than that in the control group (P < 0.05); as for the total effective rate, it was obviously higher in the experimental group after treatment than that in the control group (P < 0.05); as for the levels of CEA, CA153 and CA125, the data in the experimental group after treatment were much lower than the control group (P < 0.05). CONCLUSION: Radioactive seed 125I implantation under CT-guidance can effectively improve the effect of the treatment of breast cancer bone metastases. It has curative efficacy and it is worth promoting and using.

Combinatorial cetuximab targeted polymeric nanocomplexes reduce PRC1 level and abrogate growth of metastatic hepatocellular carcinoma in vivo with efficient radionuclide uptake.

Hepatocellular carcinoma (HCC) is the most aggressive form of cancer with poor drug responses. Developing an effective drug treatment remains a major unmet clinical need for HCC. We report a comprehensive study of combinatorial Cetuximab (Cet) targeted polymeric poly(D, L-lactide-co-glycolide)-b-poly(ethylene glycol) nanocomplexes delivery of Combretastatin A4 (CA4) and 2-Methoxyestradiol (2ME) (Cet-PLGA-b-PEG-CA4 NP + Cet-PLGA-b-PEG-2ME NP) against metastatic HCC in SCID mice. 125I-Cet-PLGA-b-PEG NP showed potent accumulation and retention in HCC tumors with longer circulation time up to 48 h (18 ±â€¯1.0% ID/g, P < .0001). Combinatorial treatment with targeted polymeric nanocomplexes presented significant tumor growth inhibition (85%, P < .0001) than the free drug combinatorial counterpart, effectively inhibited orthotopic HCC and prevented lung metastasis. Combinatorial nanocomplexes treatment significantly blocked PRC1, a novel target of therapeutic response against HCC. Thus, the combinatorial cetuximab-targeted polymeric nanocomplexes possess superior antitumor activity against metastatic HCC and provide supports for the clinical translation ahead.

Development of Low Molecular Weight Ligands for Integrin αvß3.

We designed and synthesized non-peptide organic molecular ligands for integrin αvß3. Candidate ligands featured amidino analog and carboxy groups as binding sites on either side of a spacer, which consisted of benzophenone or an analog, such as diphenyl sulfide, diphenyl sulfoxide, diphenyl sulfone, or diphenyl ether. Competitive binding assays to integrin αvß3 with respect to [125I]echistatin were used to determine inhibitory activity of the synthetic ligands. Ligands bearing 2-aminobenzimidazoyl and glycyl groups separated by a benzophenone spacer demonstrated more potent binding than did a linear Arg-Gly-Asp (RGD) tripeptide that represents the native integrin αvß3 binding motif. Ligands possessing 2-aminobenzimidazoyl and carboxy groups and diphenyl sulfoxide or diphenyl ether spacers inhibited binding of [125I]echistatin with IC50 values similar to that of the linear RGD tripeptide.

In vivo and in vitro binding of [125 I]I-R-(+)-TISCH: A dopamine D1 receptor ligand for studying pancreatic ß-cell mass.

Diabetes mellitus (DM) and insulinoma are mainly affected by the status of pancreatic ß-cell mass (BCM). Development of imaging agents for BCM allows to study pancreatic ß cells and the relationship between ß cells and DM or insulinoma. In this study, we investigated the density of dopamine D1 receptor on the ß cells and measured BCM by statistical image processing. The pancreatic uptakes of [125 I]I-R-(+)-7-chloro-8-hydroxy-1-(3'-iodopheny1)-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine ([125 I]I-R-(+)-TISCH), dopamine D1 receptor tracer, in normal and diabetic rats displayed significant differences at 30 min (1.11 ± 0.08% ID/g vs. 0.63 ± 0.09% ID/g, p < 0.0001). In the presence of SCH23390, the pancreatic uptake of [125 I]I-R-(+)-TISCH at 30 min in normal rats was lower (1.01 ± 0.04% ID/g, p < 0.05). Although the blocking was not complete, [125 I]I-R-(+)-TISCH showed specific binding signals to the pancreas. Furthermore, the uptakes of [125 I]I-R-(+)-TISCH in INS-1 cells were reduced in the presence of SCH23390 at different concentrations. [125 I]I-R-(+)-TISCH displayed a respectable uptake in insulinoma. Overall, [125 I]I-R-(+)-TISCH provided specific binding signals to pancreatic ß cells. Although the specific signal may not be sufficient for imaging in vivo, the dopamine D1 receptor can still be considered as a potential target for studying BCM. Further investigation will be required to optimize the ligand.