The relationship between splenic dose and radiation-induced lymphopenia.

Lymphocytes, which are highly sensitive to radiation, play a crucial role in the body's defense against tumors. Radiation-induced lymphopenia has been associated with poorer outcomes in different cancer types. Despite being the largest secondary lymphoid organ, the spleen has not been officially designated as an organ at risk. This study hypothesizes a connection between spleen irradiation and lymphopenia and seeks to establish evidence-based dosage limits for the spleen. We retrospectively analyzed data from 96 patients with locally advanced gastric cancer who received postoperative chemoradiotherapy (CRT) between May 2010 and May 2017. Complete blood counts were collected before, during and after CRT. We established a model for predicting the minimum absolute lymphocyte count (Min ALC) and to investigate potential associations between spleen dosimetric variables and Min ALC. The median follow-up was 60 months. The 5-year overall survival (OS) and disease-free survival (DFS) were 65.2% and 56.8%, respectively. The median values of pre-treatment ALC, Min ALC and post-treatment ALC were 1.40 × 109, 0.23 × 109 and 0.28 × 109/L, respectively. Regression analysis confirmed that the primary tumor location, number of fractions and spleen V5 were significant predictors of Min ALC during radiation therapy. Changes in ALC (ΔALC) were identified as an independent predictor of both OS and DFS. Spleen V5 is an independent predictor for Min ALC, and the maximum dose of the spleen is associated with an increased risk of severe lymphopenia. Therefore, these doses should be restricted in clinical practice. Additionally, ΔALC can serve as a prognostic indicator for adjuvant radiotherapy in gastric cancer.

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma: A case report.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with limited effective treatment especially after first-line chemotherapy. The human epidermal growth factor receptor 2 (HER-2) immunohistochemistry (IHC) positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC. CASE SUMMARY: We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn't have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment. A novel combination therapy PRaG 3.0 of RC48 (HER2-antibody-drug conjugate), radiotherapy, PD-1 inhibitor, granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month. She had not developed any grade 2 or above treatment-related adverse events at any point. Percentage of peripheral CD8+Temra and CD4+Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy. CONCLUSION: PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Evaluation of the efficacy and safety of a precise thymalfasin-regulated PRaG regimen for advanced refractory solid tumours: protocol for the open-label, prospective, multicentre study (PRaG5.0 study).

INTRODUCTION: The PRaG regimen, which consists of hypofractionated radiotherapy combined with a programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitor and granulocyte-macrophage colony stimulating factor (GM-CSF), has been demonstrated to have a survival benefit in patients with advanced solid tumours who have failed at least two lines of treatment. Nonetheless, lymphopenia poses an impediment to the enduring efficacy of PD-1/PD-L1 inhibitor therapy. Adequate lymphocyte reserves are essential for the efficacy of immunotherapy. Coupling the PRaG regimen with immunomodulatory agents that augment the number and functionality of lymphocytes may yield further survival benefits in this cohort of patients. OBJECTIVE: The aim of this study is to investigate the effectiveness and safety of a meticulously thymalfasin-controlled PRaG regimen in patients with advanced and chemotherapy-resistant solid tumours. METHODS AND ANALYSIS: The study has a prospective, single-arm, open-label, multicentre design and aims to recruit up to 60 patients with histologically confirmed advanced solid tumours that have relapsed or metastasised. All eligible patients will receive a minimum of two cycles of the PRaG regimen comprising thymalfasin followed by maintenance treatment with a PD-1/PD-L1 inhibitor and thymalfasin for 1 year or until disease progression. Patients will be monitored according to the predetermined protocol for a year or until disease progression after initiation of radiotherapy. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the Second Affiliated Hospital of Soochow University, on 25 November 2022 (JD-LK-2022-151-01) and all other participating hospitals. Findings will be disseminated through national and international conferences. We also plan to publish our findings in high-impact peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05790447.

Effect of Cyclosporin H on ischemic injury and neutrophil infiltration in cerebral infarct model of rats via PET imaging.

BACKGROUND: Brain ischemia-reperfusion injury is a complex process, and neuroinflammation is an important secondary contributing pathological event. Neutrophils play major roles in ischemic neuroinflammation. Once activated, neutrophils express formyl peptide receptors (FPRs), which are special receptors of a class of chemoattractants and may be potential targets to regulate the activity of neutrophils and control cerebral ischemic injury. This study was aimed to explore the ameliorating effect of Cyclosporin H (CsH), a potent FPR antagonist, on brain ischemic injury by inhibiting the activation and migration of neutrophils, and improving cerebral blood flow. METHODS: We employed a middle cerebral artery occlusion (MCAO) Model on rats and performed behavioral, morphological, and microPET imaging assays to investigate the potential restoring efficacy of CsH on cerebral ischemic damages. Peptide N-cinnamoyl-F-(D)L-F-(D)L-F (cFLFLF), an antagonist to the neutrophil FPR with a high binding affinity, was used for imaging neutrophil distribution. RESULTS: We found that CsH had similar effect with edaravone on improving the neurobehavioral deficient symptoms after cerebral ischemia-reperfusion, and treatment with CsH also alleviated ischemic cerebral infarction. Compared with the MCAO Model group, [18F]FDG uptake ratios of the CsH and edaravone treatment groups were significantly higher. The CsH-treated groups also showed significant increases in [18F]FDG uptake at 144 h when compared with that of 24 h. This result indicates that like edaravone, treatment with both doses of CsH promoted the recovery of blood supply after cerebral ischemic event. Moreover, MCAO-induced cerebral ischemia significantly increased the radiouptake of [68Ga]Ga-cFLFLF at 72 h after ischemia-reperfusion operation. Compared with MCAO Model group, radiouptake values of [68Ga]-cFLFLF in both doses of CsH and edaravone groups were all decreased significantly. These results showed that both doses of CsH resulted in a similar therapeutic effect with edaravone on inhibiting neutrophil infiltration in cerebral infarction. CONCLUSION: Potent FPR antagonist CsH is promisingly beneficial in attenuating neuroinflammation and improving neurobehavioral function against cerebral infarction. Therefore, FPR may become a novel target for regulating neuroinflammation and improving prognosis for ischemic cerebrovascular disorders.

Exploring active ingredients of anti-osteoarthritis in raw and wine-processed Dipsaci Radix based on spectrum-effect relationship combined with chemometrics.

ETHNOPHARMACOLOGICAL RELEVANCE: Dipsaci Radix (DR) is the dry root of the Dipsacus asper Wall. ex DC., which has the function of tonifying the liver and kidney, continuing tendons and bones, and regulating blood vessels. However, there are few reports on the main active ingredients. AIM OF THE STUDY: This study aimed to find the main active components of DR in the treatment of osteoarthritis (OA) by spectrum-effect relationship and compare the differences between RDR and WDR. MATERIALS AND METHODS: Firstly, the high-performance liquid chromatography (HPLC) method was used to establish the fingerprint of DR, and 10 peaks of them were determined by UPLC-Q-TOF/MS. Then, the OA rat model was established by injecting sodium iodoacetate to study the effect of DR on OA. The spectrum-effect relationship was analyzed by grey relational analysis (GRA) and Pearson correlation analysis. RESULTS: According to the pharmacological results, compared with the model group, the cartilage score, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), and Mankin score of rats in low, medium and high dose groups were decreased, and the therapeutic effect of wine-processed DR tended to be better than raw DR at the same dose. Finally, the active components of DR were preliminarily determined as 4 (loganic acid), 6 (chlorogenic acid), 8 (caffeic acid), 14 (dipsanoside B), 16, and 17 (asperosaponin VI) which had a large correlation in GRA and Pearson correlation analysis. CONCLUSION: This study established the spectrum-effect relationship between the raw and wine-processed DR for the first time, which provided a theoretical basis for the study of the pharmacodynamic substance basis of DR before and after processing. This research provided a reference for the subsequent study of DR.

Design of fractional order PID controller based on minimum variance control and application of dynamic data reconciliation for improving control performance.

Fractional order PID (FOPID) has received much attention in recent years and has been applied in different fields. However, the parameter tuning of FOPID is a tough problem. In order to design an optimal FOPID controller, a parameter tuning method based on minimum variance control (MVC) rule is proposed in both SISO and MIMO control systems Considering the influence of measurement noise with Gaussian and non-Gaussian distribution, which is generally ignored in the controller design based on MVC rule, this paper applies dynamic data reconciliation (DDR) technology to suppress its influence and improve the control performance of the designed FOPID. In the case of considering Gaussian and non-Gaussian distributed measurement noise, SISO and MIMO control systems are employed to verify the effectiveness of the proposed FOPID parameter tuning and DDR method. The results show that the designed FOPID improves the performance of the control system, and the DDR technology suppresses the negative effect of measurement noise and improves the control performance of the designed FOPID.

PRaG Therapy of Refractory Metastatic Gastric Cancer: A Case Report.

Patients with metastatic gastric cancer had limited treatments and often had a somber prognosis, especially when patients were unable to tolerate high-intensity cytotoxic treatment due to poor physical condition or organ dysfunction after the failure of standard therapy. Here, we reported a metastatic and proficient mismatch repair (pMMR) gastric adenocarcinoma patient with the Eastern Cooperative Oncology Group (ECOG) performance status score of 2 associated with hypoproteinemia and fatigue, and poor appetite that was unable to tolerate high-intensity therapy after several chemotherapy regimens and anti-angiogenic therapy. After receiving novel triple-combination therapy, which consists of PD-1 inhibitor, Radiotherapy and Granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy (PRaG for short), the patient achieved a complete response (CR) with a progression-free survival time of 14 months, and ECOG performance status score improved from 2 to 0. A significant systemic effect was observed in this case and the PRaG triple-combination therapy might provide a novel treatment strategy for metastatic pMMR gastric cancer patients.

Glaucocalyxin a protect liver function via inhibiting platelet over-activation during sepsis.

BACKGROUND: Rabdosia japonica (Burm. f.) var. glaucocalyx (Maxim.) is a perennial herb, and is traditionally used as folk medicine for treating inflammatory diseases and cancer. Gaucocalyxin A (GLA) is an ent­kaurane diterpenoid that is isolated from the aerial parts of R. japonica (Burm. f.) var. glaucocalyx (Maxim.). In a recent study, we found that GLA protects against acute liver dysfunction induced by Escherichia coli, which is likely related to its anti-inflammatory effects. However, the mechanism by which GLA protects liver injury during sepsis is unknown. AIM: To evaluate the anti-inflammatory function of GLA and its regulatory effect on platelet function. METHOD: An in vivo model of sepsis was established by inoculating mice with E. coli. Live function and platelet activation were evaluated through standard assays. The levels of pro-inflammatory factors were measured through ELISA and qRT-PCR. RESULTS: GLA alleviated liver dysfunction in the mouse model of sepsis. GLA-treated mice displayed lower complement activation and liver dysfunction after E. coli infection. GLA alleviated the decrease in peripheral platelet counts by inhibiting their clearance by Kupffer cells in liver. Furthermore, GLA inhibited platelet activation through the RIP1/RIP3/AKT pathway and downregulated C3aR expression on the platelets, thereby inhibiting liver injury and dysfunction due to excessive complement activation. CONCLUSION: GLA can inhibit platelet activation by reducing surface expression of C3aR, which protect the liver from injury induced by excessive complement activation. GLA is a novel therapeutic agent for controlling sepsis-related liver dysfunction.

Unscented Kalman Filter-Based Robust State and Parameter Estimation for Free Radical Polymerization of Styrene with Variable Parameters.

The free radical polymerization of styrene (FRPS) is a complex process system with uncertain parameters in its mechanistic model. When the reaction conditions are switched, or the reaction process generates faults, the parameters will change. Therefore, state and parameter estimation (SPE) becomes an important part of the process monitoring and process control for free radical polymerization of styrene. The unscented Kalman filter (UKF) is widely used for nonlinear process systems, but it rarely considers the problem of model parameter uncertainty. UKF can be used for SPE, called UKF-based SPE (UKF-SPE), where the parameters are usually estimated simultaneously as an extension of the state space. However, when the parameters change with system switching, the traditional UKF-SPE cannot detect and track the parameter changes in time, and inaccurate parameters generate modeling errors. To deal with the problem, a UKF-based robust SPE method (UKF-RSPE) for the free radical polymerization of styrene with variable parameters is proposed, introducing a parameter testing criterion based on hypothesis testing and moving windows to directly detect whether the parameters have changed. Based on the detection results, a gradient descent method with adaptive learning rate is used to iteratively update the parameters to speed up the tracking of the parameters and to obtain more accurate parameters and states. Finally, the proposed UKF-based robust SPE is applied to free radical polymerization of styrene in a jacketed continuous stirred tank reactor. The experimental results verify the effectiveness and robustness of the method, which can track the parameters faster and obtain more accurate states.

AL355338 acts as an oncogenic lncRNA by interacting with protein ENO1 to regulate EGFR/AKT pathway in NSCLC.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a malignancy with considerable morbidity and mortality. Abnormal metabolism is a hallmark of cancer; however, the mechanism of glycolysis regulation in NSCLC progression is not completely understood. Recent studies suggest that some dysregulated long non-coding RNAs (lncRNAs) play important roles in tumor metabolic reprogramming. METHODS: To identify glycolysis-associated-lncRNAs in NSCLC, we compared RNA-sequencing results between high 18F-fluorodeoxyglucose (FDG)-uptake NSCLC tissues and paired paratumor tissues. The transcript abundance of AL355338 in 80 pairs of clinical samples was evaluated by quantitative real-time PCR assay and fluorescence in situ hybridization. The biological role of AL355338 on NSCLC cells were evaluated by functional experiments in vitro and in vivo. Moreover, RNA pull-down, mass spectrometry and RNA immunoprecipitation (RIP) assays were used to identify the protein interacted with AL355338. Co-immunoprecipitation, in situ proximity ligation assays and western blotting were applied to define the potential downstream pathways of AL355338. RESULTS: AL355338 was an upregulated glycolysis-associated lncRNA in NSCLC. Functional assays revealed that AL355338 was critical for promoting aerobic glycolysis and NSCLC progression. Mechanistic investigations showed that AL355338 directly bound with alpha-enolase (ENO1) and enhanced the protein's stability by modulating its degradation and ubiquitination. A positive correlation was observed between AL355338 and ENO1 in NSCLC, and ENO1 was subsequently confirmed to be responsible for the oncogenic role of AL355338. Furthermore, AL355338 was capable of modulating ENO1/EGFR complex interaction and further activating EGFR-AKT signaling. CONCLUSIONS: This study indicates that AL355338 confers an aggressive phenotype to NSCLC, and targeting it might be an effective therapeutic strategy.

Rapid Quality Identification of Decoction Pieces of Crude and Processed Corydalis Rhizoma by Near-Infrared Spectroscopy Coupled with Chemometrics.

In order to identify the quality of crude and processed Corydalis Rhizoma decoction pieces, the research established a simple, fast, reliable, and validated near-infrared qualitative and quantitative model combined with chemometrics. 51 batches of crude and 40 batches of processed Corydalis Rhizoma from the Zhejiang and Jiangsu provinces of China were collected and analyzed. Crude and processed Corydalis Rhizoma samples were crushed to obtain NIR spectra. The content of seven alkaloids in crude and processed Corydalis Rhizoma was determined by high-performance liquid chromatography (HPLC). Pretreatment methods were screened such as normalization methods, offset filtering methods, and smoothing. Combined with partial least squares-discriminant analysis (PLS-DA) and partial least squares (PLS), the qualitative and quantitative models of crude and processed Corydalis Rhizoma were established, and the correlation coefficient (R 2), root mean square error of calibration (RMSEC), and root mean square error of prediction (RMSEP) were used as evaluation indexes. Tetrahydropalmatine was used as an example for screening pretreatment methods; the results showed that MSC combined with the second derivative and no smoothing and the model with the wavelength range of 10000-5000 cm-1 had the best predictive ability and applied to all seven alkaloid components. Among them, the correlation coefficients were all higher than 0.99, and RMSEC and RMSEP were all less than 1%. The qualitative and quantitative model of the seven alkaloids in Corydalis Rhizoma can effectively identify the crude and processed Corydalis Rhizoma and determine the content of the seven alkaloids. By studying the NIR qualitative and quantitative models of crude and processed Corydalis Rhizoma, we can achieve rapid discrimination and quantitative prediction of crude and processed Corydalis Rhizoma. These methods can greatly improve the efficiency of traditional Chinese medicine analysis and provide a strong scientific basis for the quality identification and control of traditional Chinese medicine.

Pretargeted radioimmunoimaging with a biotinylated D-D3 construct and 99mTc-DTPA-biotin: strategies for early diagnosis of small cell lung cancer.

OBJECTIVE: Pro-gastrin releasing peptide (ProGRP) plays an oncogenic role in small cell lung cancer (SCLC). The anti-ProGRP(31-98) monoclonal antibody D-D3 can selectively accumulate in SCLC xenografts in nude mice. This study evaluated the effectiveness of a new pretargeting procedure for the early diagnosis of SCLC. METHODS: D-D3 was radiolabeled with technetium-99m (99mTc) using a three-step pretargeting method. Mice with SCLC xenografts were treated with different labeling regimens, and the biodistribution and radioimmunoimaging were explored. The percentage injected dose per gram (%ID/g) in various organs, tumor/non-tumor (T/NT) ratio, and tumor/background (T/B) ratio were also calculated. RESULTS: In vivo distribution experiments revealed that 99mTc-DTPA-biotin was metabolized in the liver and kidney, with rapid elimination in the blood. The T/B ratio was highest in mice treated with biotinylated antibody D-D3 + avidin + 99mTc-DTPA-biotin. Single-photon emission computerized tomography imaging further confirmed that the T/B ratio was highest in this group at all time points. CONCLUSIONS: In contrast to directly labeled D-D3, pretargeting technology displayed specific enhancement and signal amplification in tumors, which could increase the target tumor uptake of 99mTc and provide a new approach for the early diagnosis of SCLC.

Particle filter combined with data reconciliation for nonlinear state estimation with unknown initial conditions in nonlinear dynamic process systems.

State estimation is very crucial for process control and optimization in dynamic processes. The particle filter (PF) is a novel and suitable technique for state estimation of nonlinear dynamic process systems. Conventional PFs for nonlinear dynamic process systems rely on the known initial conditions for state variables, such as the known probability density function (PDF) of initial states or the known values of initial states, but the initial conditions of a nonlinear dynamical system are usually unknown in actual industrial processes. In this paper, a novel methodology, PF combined with data reconciliation, is proposed and applied to nonlinear dynamic process systems for state estimation with unknown initial conditions. The measurement test criterion and data reconciliation with sequentially increasing data information are proposed to derive reliable initial values of the state variables under sufficient information of measurements. The interactive information between PF and data reconciliation problems can improve the initial values iteratively. Finally, accurate results of state estimation can be achieved. The effectiveness of the methodology is demonstrated through two nonlinear dynamic systems.

Prognostic value of baseline 18 F-FDG PET/CT metabolic parameters in paediatric lymphoma.

INTRODUCTION: In the present study, we aimed to investigate the prognostic value of metabolic parameters, including maximum standardized uptake value (SUVmax ), total metabolic tumour volume (tMTV) and total lesion glycolysis (TLG), measured at baseline 18 F-FDG PET/CT in paediatric lymphoma. METHODS: From March 2013 to April 2019, 47 patients with paediatric lymphoma, including 38 males and nine females with an average age of 14.87 years, who underwent 18 F-FDG PET/CT scan prior to treatment were retrospectively included in this study. SUVmax , MTV and TLG were recorded. Survival curves were established according to the Kaplan-Meier curves and log-rank test. Mann-Whitney U-test was used to assess differences in metabolic parameters between different clinical outcomes. RESULTS: The median follow-up time was 36 months (range of 3-74 months). The 2-year progression-free survival (PFS) of the low TLG and high TLG groups was 95.24% (20/21) and 57.69% (15/26), respectively (P = 0.004). TLG and tMTV were significantly higher in progression-free patients compared with the progression group. Univariate analysis showed that B symptoms (P = 0.014), effusion (P = 0.010), tMTV (P = 0.008) and TLG (P = 0.004) were the predictive factors for PFS. The tMTV (P = 0.005), TLG (P = 0.005) and effusion (P = 0.003) were associated with OS. Multivariate analysis revealed that TLG was the only independent prognostic factor for PFS (HR = 11.133, 95% CI = 1.435-86.405, P = 0.021). CONCLUSIONS: Collectively, TLG of baseline 18 F-FDG PET/CT was an independent prognostic factor for PFS in patients with paediatric lymphoma.

An Evaluation of HER2-Positive Ovarian Carcinoma Xenografts: From a Novel Therapy to a Noninvasive Monitoring Method.

PURPOSE: Overexpression of the HER2/neu (HER2) is linked to an adverse outcome in ovarian cancer. Short-interfering RNA (siRNA) is a HER2 inhibitor, which in combination with chemotherapy improves survival rate. The aim of this study was to evaluate the efficacy of adenovirus mediated HER2-siRNA in combination with cisplatin (Ad-HER2-siRNA+DDP) on treating HER2-positive ovarian cancer xenografts and explore the effectiveness of 131I-Herceptin immunoSPECT imaging for monitoring the tumor's progression. METHODS: Mice with ovarian cancer xenografts were treated with different therapy regimens and imaged at 1, 4, 8, 12, 24, 48, 72, and 96 h postinjection with 131I-Herceptin. Concurrently, the tumor/background (T/B) ratios were calculated. In addition, HER2 protein expression levels were determined by immunohistochemistry (IHC). RESULTS: The in vivo therapy experiments revealed that tumor weight and volume of Ad-HER2-siRNA+DDP group was the least of all. The IHC results further confirmed that HER2 protein level was significantly downregulated in this group. The results of SPECT imaging showed that the T/B ratios at each time point in Ad-HER2-siRNA +DDP group was the lowest (p < 0.05). CONCLUSIONS: The data demonstrate that the growth of xenografts of human ovarian cancer with high expression of HER2 could be inhibited effectively by Ad-HER2-siRNA+DDP. 131I-Herceptin had potential use for noninvasive imaging of HER2 expression.

Preliminary radioimmunoimaging and biodistribution of ¹³¹iodine-labeled single-chain antibody fragment against progastrin-releasing peptide(31₋98) in small cell lung cancer xenografts.

BACKGROUND: Monoclonal antibodies (mAbs) such as DD3, raised against progastrin-releasing peptide(31-98) (ProGRP (31-98)) antigen, have been used to target small cell lung cancer (SCLC). However, as an intact mAb, DD3 is cleared slowly from the body, with an optimal radioimmunoimaging time of 72 hours. More recently, a single-chain antibody fragment has demonstrated reduced excretion time in blood and normal tissues and is increasingly used in diagnostic cancer research. Thereby, it potentially increases the radioimmunoimaging efficacy. However, there have been few studies with this antibody fragment. The aim of this study was to characterize the preliminary radioimmunoimaging and biodistribution of (131)I-anti-ProGRP(31-98) scFv in nude mice bearing SCLC xenografts. METHODS: Anti-ProGRP(31-98) scFv was used to detect ProGRP expression by flow cytometry analysis and immunohistochemistry. (131)I-anti-ProGRP(31-98) scFv was injected intravenously into healthy Kunming mice and the percentage injected dose per gram (%ID/g) in various organs was calculated. Similarly, the %ID/g and tumor/non-tumor ratio in xenograft-bearing mice was calculated. After injection of (131)I-anti-ProGRP(31-98) scFv, treated mice were imaged at 1, 24, and 30 hours. Then the tumor/base ratios were calculated. RESULTS: ProGRP was highly expressed in NCI-H446 cells and xenograft tissue. The metabolism of (131)I-anti-ProGRP(31-98) scFv in healthy mice was consistent with a first-order and two-compartment model; T1/2α and T1/2ß were 10.2 minutes and 5 hours 18 minutes, respectively. The %ID/g of (131)I-anti-ProGRP(31-98) scFv in xenografts was much higher than in healthy tissues at 12 hours after injection, reaching a maximum of (5.38±0.92) %ID/g at 24 hours. Successful imaging of xenograft tissue was achieved as early as 1 hour post-injection and persisted until 30 hours, with 24 hours proving optimal. CONCLUSION: (131)I-anti-ProGRP(31-98) scFv shows highly selective tumor uptake with low accumulation in normal tissues and rapid blood clearance, indicating that it could be a promising agent for SCLC radioimmunoimaging.

Biodistribution and preparation of technetium-99m-labeled D-D3 monoclonal antibody against pro-gastrin-releasing peptide (31₋98) in mice.

BACKGROUND: We previously reported that iodine-131((131)I)-labeled anti-pro-gastrin-releasing peptide (ProGRP(31-98)) monoclonal antibody D-D3 could selectively accumulate in the tumor sites of nude mice bearing small cell lung cancer (SCLC) xenografts. However, (131)I-D-D3 was cleared slowly from the body, and the best radioimmunoimaging time for SCLC was 72 - 96 hours after injection. The aims of this study were to radiolabel anti-ProGRP(31-98) D-D3 monoclonal antibody with technetium-99m ((99m)Tc) and to investigate the biodistribution of this antibody in healthy ICR mice. METHODS: D-D3 was labeled with (99m)Tc via the 2-mercaptoethanol reduction method. (99m)Tc-D-D3 was purified by the gel column separation method. The labeling efficiency and radiochemical purity were measured by thin-layer chromatography. The immunological activity of (99m)Tc-D-D3 was determined with cell conjugation assays. (99m)Tc-D-D3 was injected into healthy ICR mice via a tail vein, and all the healthy ICR mice were sacrificed by cervical dislocation at a designated time. Then, the blood and major organs were removed and weighed, and counted in a gamma scintillation counter to determine the percentage of the injected dose per gram (%ID/g). RESULTS: The labeling rate and the radiochemical purity of (99m)Tc-D-D3 were (73.87 ± 2.89)% and (94.13 ± 4.49)%, respectively. The immunobinding rates of (99m)Tc-D-D3 to the human small cell lung cancer NCI-H446 cell line and lung adenocarcinoma A549 cell line were (81.2 ± 2.37)% and (24.3 ± 1.46)%, respectively. The distribution data of normal ICR mice demonstrated that (99m)Tc-D-D3 was mainly distributed in the liver, kidney and lung, and less in the brain tissue and muscle. CONCLUSIONS: (99m)Tc-D-D3 antibody not only had high radiochemical purity, but also had good stability both in vitro and in vivo, and maintained good immunological activity. (99m)Tc-D-D3 was metabolized mainly in the kidney and liver, and the blood radioactivity decreased rapidly. Thus, (99m)Tc-D-D3 is conducive to the radioimmunoimaging of SCLC.

[Values of (99m)TcO(-)(4)thyroid imaging plus ultrasonography in the differential diagnoses of thyroid nodules].

OBJECTIVE: To evaluate the diagnostic values of (99m)TcO(-)(4) thyroid imaging plus ultrasonography in the differentiation of benign and malignant thyroid nodules. METHODS: (99m)TcO(-)(4) thyroid imaging and ultrasonography were performed for 114 patients with 125 thyroid nodules. And the examination results were compared with the post-operative pathological findings. RESULTS: (1) Among 125 thyroid nodules, there were thyroid adenoma (n = 64, 51.2%), thyroid cancer (n = 30, 24.0%) and other thyroid diseases (n = 31, 24.8%). On thyroid images, 73.6% of them were of cold nodules. And among these cold nodules, 25.0% were of thyroid cancer. Among the ultrasonic results, 125 nodules were predominantly of solid nodules and mixed solid and cystic nodules while the malignant rate of solid nodules was the highest. (2) The malignant rate of solid cool or cold nodules was greater than those of mixed solid and cystic cool or cold nodules (P < 0.005). (3)In solid cool or cold nodules with a diameter of ≥ 2.0 cm, thyroid cancer accounted for 62.5%. CONCLUSION: The combination of (99m)TcO(-)(4) thyroid imaging and ultrasonography may help to evaluate the (99m)TcO(-)(4) uptaking functions of thyroid nodules so that it plays an important role in the differentiation of benign and malignant thyroid nodules.