Direct attenuation correction for 99mTc-3PRGD2 chest SPECT lung cancer images using deep learning.

Introduction: The attenuation correction technique of single photon emission computed tomography (SPECT) images is essential for early diagnosis, therapeutic evaluation, and pharmacokinetic studies of lung cancer. 99mTc-3PRGD2 is a novel radiotracer for the early diagnosis and evaluation of treatment effects of lung cancer. This study preliminary discusses the deep learning method to directly correct the attenuation of 99mTc-3PRGD2 chest SPECT images. Methods: Retrospective analysis was performed on 53 patients with pathological diagnosis of lung cancer who received 99mTc-3PRGD2 chest SPECT/CT. All patients' SPECT/CT images were reconstructed with CT attenuation correction (CT-AC) and without attenuation correction (NAC). The CT-AC image was used as the reference standard (Ground Truth) to train the attenuation correction (DL-AC) SPECT image model using deep learning. A total of 48 of 53 cases were divided randomly into the training set, the remaining 5 were divided into the testing set. Using 3D Unet neural network, the mean square error loss function (MSELoss) of 0.0001 was selected. A testing set is used to evaluate the model quality, using the SPECT image quality evaluation and quantitative analysis of lung lesions tumor-to-background (T/B). Results: SPECT imaging quality metrics between DL-AC and CT-AC including mean absolute error (MAE), mean-square error (MSE), peak signal-to-noise ratio (PSNR), structural similarity (SSIM), normalized root mean square error (NRMSE), and normalized Mutual Information (NMI) of the testing set are 2.62 ± 0.45, 58.5 ± 14.85, 45.67 ± 2.80, 0.82 ± 0.02, 0.07 ± 0.04, and 1.58 ± 0.06, respectively. These results indicate PSNR > 42, SSIM > 0.8, and NRMSE < 0.11. Lung lesions T/B (maximum) of CT-AC and DL-AC groups are 4.36 ± 3.52 and 4.33 ± 3.09, respectively (p = 0.81). There are no significant differences between two attenuation correction methods. Conclusion: Our preliminary research results indicate that using the DL-AC method to directly correct 99mTc-3PRGD2 chest SPECT images is highly accurate and feasible for SPECT without configuration with CT or treatment effect evaluation using multiple SPECT/CT scans.

A Pilot Study of Radiomics Models Combining Multi-Probe and Multi-Modality Images of 68Ga-NOTA-PRGD2 and 18F-FDG PET/CT for Differentiating Benign and Malignant Pulmonary Space-Occupying Lesions.

Background: This is a pilot study of radiomics based on 68Ga-NOTA-PRGD2 [NOTA-PEG4-E[c(RGDfK)]2)] and 18F-FDG PET/CT to (i) evaluate the diagnostic efficacy of radiomics features of 68Ga-NOTA-PRGD2 PET in the differential diagnosis of benign and malignant pulmonary space-occupying lesions and (ii) compare the diagnostic efficacy of multi-modality and multi-probe images. Methods: We utilized a dataset of 48 patients who participated in 68Ga-NOTA-PRGD2 PET/CT and 18F-FDG PET/CT clinical trials to extract image features and evaluate their diagnostic efficacy in the differentiation of benign and malignant lesions by the Mann-Whitney U test. After feature selection with sequential forward selection, random forest models were developed with tenfold cross-validation. The diagnostic performance of models based on different image features was visualized by receiver operating characteristic (ROC) curves and compared by permutation tests. Results: Fourteen of the 68Ga-NOTA-PRGD2 PET features between benign and malignant pulmonary space-occupying lesions had significant differences (P<0.05, Mann-Whitney U test). Eighteen of the 68Ga-NOTA-PRGD2 PET features demonstrated higher AUC values than all CT features in the differential diagnosis of pulmonary lesions. The AUC value (0.908) ​​of the three-modal feature model was significantly higher (P<0.05, permutation test) than those of the single- and dual-modal models. Conclusion: 68Ga-NOTA-PRGD2 PET features have better diagnostic capacity than CT features for pulmonary space-occupying lesions. The combination of multi-modality and multi-probe images can improve the diagnostic efficiency of models. Our preliminary clinical hypothesis of using radiomics based on 68Ga-NOTA-PRGD2 PET images and multimodal images as a diagnostic tool warrants further validation in a larger multicenter sample size.

Breast Carcinoma Shown on 99mTc-HYNIC-TOC Study Performed to Evaluate Tumor-Induced Osteomalacia.

ABSTRACT: A 74-year-old woman with a history of suspected tumor-induced osteomalacia underwent 99mTc-HYNIC-TOC scintigraphy to search potential culprit tumor. The images showed one in the middle shaft of left femur without corresponding morphology change on the CT portion of the subsequent SPECT/CT images. The patient declined surgical exploration of the left femur. Another activity was in the right breast, which was resected and pathologically confirmed as breast carcinoma. Postsurgically, the patient's symptoms were not improved. Four years later, a repeat 99mTc-HYNIC-TOC scintigraphy showed more prominent activity in the left femur with gross abnormality on the corresponding CT images.

Scintigraphic Imaging of Neovascularization With 99mTc-3PRGD2 for Evaluating Early Response to Endostar Involved Therapies on Pancreatic Cancer Xenografts In Vivo.

Background: Molecular imaging targeting angiogenesis can specifically monitor the early therapeutic effect of antiangiogenesis therapy. We explore the predictive values of an integrin αvß3-targeted tracer, 99mTc-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2), for monitoring the efficacy of Endostar antiangiogenic therapy and chemotherapy in animal models. Methods: The pancreatic cancer xenograft mice were randomly divided into four groups, with seven animals in each group and treated in different groups with 10 mg/kg/day of Endostar, 10 mg/kg/day of gemcitabine, 10 mg/kg/day of Endostar +10 mg/kg/day of gemcitabine at the same time, and the control group with 0.9% saline (0.1 ml/day). 99mTc-3PRGD2 scintigraphic imaging was carried out to monitor therapeutic effects. Microvessel density (MVD) was measured using immunohistochemical staining of the tumor tissues. The region of interest (ROI) of tumor (T) and contralateral corresponding site (NT) was delineated, and the ratio of radioactivity (T/NT) was calculated. Two-way repeated-measure analysis of variance (ANOVA) was used to assess differences between treatment groups. Results: Tumor growth was significantly lower in treatment groups than that in the control group (p < 0.05), and the differences were noted on day 28 posttreatment. The differences of 99mTc-3PRGD2 uptakes were observed between the control group and Endostar group (p = 0.033) and the combined treatment group (p < 0.01) on day 7 posttreatment and on day 14 posttreatment between the control group and gemcitabine group (p < 0.01). The accumulation of 99mTc-3PRGD2 was significantly correlated with MVD (r = 0.998, p = 0.002). Conclusion: With 99mTc-3PRGD2 scintigraphic imaging, the tumor response to antiangiogenic therapy, chemotherapy, and the combined treatment can be observed at an early stage of the treatments, much earlier than the tumor volume change. It provides new opportunities for developing individualized therapies and dose optimization.

Semi-Supervised Domain Adaptation via Asymmetric Joint Distribution Matching.

An intrinsic problem in domain adaptation is the joint distribution mismatch between the source and target domains. Therefore, it is crucial to match the two joint distributions such that the source domain knowledge can be properly transferred to the target domain. Unfortunately, in semi-supervised domain adaptation (SSDA) this problem still remains unsolved. In this article, we therefore present an asymmetric joint distribution matching (AJDM) approach, which seeks a couple of asymmetric matrices to linearly match the source and target joint distributions under the relative chi-square divergence. Specifically, we introduce a least square method to estimate the divergence, which is free from estimating the two joint distributions. Furthermore, we show that our AJDM approach can be generalized to a kernel version, enabling it to handle nonlinearity in the data. From the perspective of Riemannian geometry, learning the linear and nonlinear mappings are both formulated as optimization problems defined on the product of Riemannian manifolds. Numerical experiments on synthetic and real-world data sets demonstrate the effectiveness of the proposed approach and testify its superiority over existing SSDA techniques.

Domain Adaptation by Joint Distribution Invariant Projections.

Domain adaptation addresses the learning problem where the training data are sampled from a source joint distribution (source domain), while the test data are sampled from a different target joint distribution (target domain). Because of this joint distribution mismatch, a discriminative classifier naively trained on the source domain often generalizes poorly to the target domain. In this paper, we therefore present a Joint Distribution Invariant Projections (JDIP) approach to solve this problem. The proposed approach exploits linear projections to directly match the source and target joint distributions under the L2-distance. Since the traditional kernel density estimators for distribution estimation tend to be less reliable as the dimensionality increases, we propose a least square method to estimate the L2-distance without the need to estimate the two joint distributions, leading to a quadratic problem with analytic solution. Furthermore, we introduce a kernel version of JDIP to account for inherent nonlinearity in the data. We show that the proposed learning problems can be naturally cast as optimization problems defined on the product of Riemannian manifolds. To be comprehensive, we also establish an error bound, theoretically explaining how our method works and contributes to reducing the target domain generalization error. Extensive empirical evidence demonstrates the benefits of our approach over state-of-the-art domain adaptation methods on several visual data sets.

Natural Products, Traditional Uses and Pharmacological Activities of the Genus Biebersteinia (Biebersteiniaceae).

Medicinal plants have been known as a rich source of natural products (NPs). Due to their diverse chemical structures and remarkable pharmacological activities, NPs are regarded as important repertoires for drug discovery and development. Biebersteinia plant species belong to the Biebersteiniaceae family, and have been used in folk medicines in China and Iran for ages. However, the chemical properties, bioactivities and modes of action of the NPs produced by medicinal Biebersteinia species are poorly understood despite the fact that there are only four known Biebersteinia species worldwide. Here, we reviewed the chemical classifications and diversity of the various NPs found in the four known Biebersteinia species. We found that the major chemical categories in these plants include flavonoids, alkaloids, phenylpropanoids, terpenoids, essential oils and fatty acids. We also discussed the anti-inflammatory, analgesic, antibacterial, antioxidant, antihypertensive and hypoglycemic effects of the four Biebersteinia species. We believe that the present review will facilitate the exploration of traditional uses and pharmacological properties of Biebersteinia species, extraction of the NPs and elucidation of their molecular mechanisms, as well as the development of novel drugs based on the reported properties and mode-of-action.

Simultaneous reduction of arsenic and cadmium bioavailability in agriculture soil and their accumulation in Brassica chinensis L. by using minerals.

In situ immobilization of heavy metal cations in contaminated soil using natural minerals is an attractive remediation technique. However, little research has focused on the remediation of arsenic (As) and cadmium (Cd) co-contaminated. In this work, three different crystal structures and chemical compositions minerals, zeolite; bentonite; and dolomite, were applied to simultaneously reduce the uptake of As and Cd in Brassica chinensis L., and the mechanism on reducing As and Cd bioavailability in soil were also investigated. The results showed that the three minerals decreased the bioavailability of As and Cd and restrained their uptake by Brassica chinensis L. with the order followed bentonite > zeolite > dolomite. Particularly, bentonite decreased the exchangeable As and Cd by 4.05% and 32.5% and the concentrations of As and Cd in shoots of Brassica chinensis L. by 36.2% and 64.6%, as compared with the controls. Moreover, with the addition of minerals increased, the dry biomass of Brassica chinensis L. and the rhizosphere microbial functional diversity increased significantly, and the highest biomass increased by 289% at 4.0% addition of bentonite. Correlation analysis indicated that the uptake of As and Cd was positive with the available Cd and As in soil, and was negative with soil pH and available N. Furthermore, the Scanning Electron Microscopy-Energy Dispersive Spectroscopy and Fourier Transform Infrared Spectroscopy analysis illustrated the interaction between minerals and Cd mainly involved ion-exchange and adsorption, while As was mainly immobilized by calcium and magnesium through forming precipitation. In conclusion, this present study implied that the bentonite can be recommended as the more effective amendment to immobilize metal (loid)s in soil and thereby reduce the exposure risk of metal (loid)s associated with grains consumption.

Hepatosplenic Tuberculosis on Pretherapy and Posttherapy FDG PET/CT.

A 65-year-old woman underwent FDG PET/CT for presumed hepatosplenic malignancy suggested by an abdominal CT. The images revealed multiple foci of intense FDG activity in both the liver and the spleen. However, a splenic biopsy result revealed no malignant cells, and either tuberculosis or sarcoidosis was proposed. Following an incomplete antituberculosis therapy, a repeat FDG PET/CT showed resolution of the abnormal activity in the liver and the spleen.

[Effects of Bentonite on Chemical Forms and Bioavailability of Heavy Metals in Different Types of Farmland Soils].

A pot experiment was conducted to evaluate the effects of bentonite on the physicochemical properties of soil; chemical forms of Cd, As, V, and Cr; pakchoi (Brassica chinensis L.) growth; metal uptake; and rhizosphere microbial community in three different types of farmland soils. The results showed that bentonite decreased the exchangeable Cd in the sequence of Yellow earths (Gy, 19.44%) > Yellow-cinnamon soils (Sy, 13.85%) > Fluvo-aquic soils (Bf, 5.03%), and the content of Cd in shoots of pakchoi declined in the sequence of Gy (34.81%) > Bf (23.91%) > Sy (11.11%), compared with the controls. Compared with the controls, the exchangeable As in Bf and Sy decreased by 4.53% and 25.16%, respectively, while the exchangeable As in Gy increased by 0.57%. The exchangeable Cr was increased in the sequence of Sy (31.30%) > Gy (2.91%) > Bf (0.58%). The residual As, V, and Cr increased (except for Cr in Sy), and their uptake was also reduced in different degrees. The addition of bentonite significantly promoted the growth of pakchoi in the three soil types, especially in Bf. pakchoi biomass, root surface area, and number of root tips increased by 147.55%, 80.71%, and 124.31%, respectively, in Bf, compared with the control. In addition, bentonite reduced the content of available nitrogen, phosphorus, and organic matter; increased the content of available potassium; and increased the diversity of rhizosphere microbial community in all three soils. Therefore, bentonite could be highly recommended as a safe stabilizer in these three types of soil.

Replication Study Confirms the Association of the Common rs1800629 Variant of the TNFα Gene with Postmenopausal Osteoporosis Susceptibility in the Han Chinese Population.

BACKGROUND: Previous studies have suggested that tumor necrosis factor α (TNF-α), encoded by the TNFα gene, can increase osteoclast formation, and that specific alleles of the TNFα gene are associated with postmenopausal osteoporosis susceptibility in some populations; however, the exact molecular mechanism remains unknown. AIMS: To investigate the potential association of nineteen polymorphisms of the TNFα gene with postmenopausal osteoporosis and bone mineral density (BMD) traits in a sample of 1288 postmenopausal women from the Han Chinese population. METHODS: A total of 437 postmenopausal osteoporosis patients and 851 unrelated age-matched healthy women were recruited to the study. Single marker and haplotype based analyses were conducted to evaluate the association of nineteen single nucleotide polymorphisms (SNPs) in both patient and control groups. RESULTS: The SNP rs1800629 was identified as being highly significantly associated with postmenopausal osteoporosis after accounting for age and body mass index (p = 0.000087). In addition, the GG genotype of this SNP was associated with significantly lower measures of femoral neck BMD and lumbar spine BMD. Moreover, haplotype based analyses suggested significant association signals between the haplotype block, including rs1800629 with postmenopausal osteoporosis (p < 0.001). CONCLUSION: We have shown that a TNFα gene polymorphism, rs1800629, is highly significantly associated with postmenopausal osteoporosis and BMD in the female Han Chinese population. Additional sequencing-based studies are needed to investigate the genetic architecture of this genomic region and its relationship with osteoporosis-related phenotypes.

Long-lasting Intense Bone Tracer Activity at the Sites of Collagen Injection.

Collagen injection has been used as dermal filler in plastic and cosmetic surgery. A technetium Tc methylene diphosphonate bone scintigraphy was performed in a 47-year-old woman as part of the breast cancer evaluation. The images showed intense methylene diphosphonate activity on both sides of the frontal head, where she received collagen injection 1 year prior. The activity was visualized again in all 3 follow-up bone scans over the subsequent 3 years.

[Expression Level and Clinical Significance of VEGF, IL-17, ß2-MG and IL-35 in Patients with Multiple Myeloma].

OBJECTIVE: To explore the expression and clinical significance of VEGF, IL-17, ß2-MG and IL-35 in patients with multiple myeloma. METHODS: A total of 83 patients with multiple myeloma (MM) from January 2012 to December 2016 were enrolled in MM group, 36 healthy subjects were enrolled in control group. The levels of IL-17, IL-35 and VEGF in serum were detected by ELISA. The levels of ß2-MG in serum were measured by radioimmunoassay. The differences of different indexes between 2 groups were compared. RESULTS: The serum levels of IL-17, VEGF and ß2-MG in serum of III stage were higher than that in II stage, which was higher than that in I stage and control group (P<0.05). The levels of IL-35 in the control group were significantly higher than those in the I,II,III stage group (P<0.05). The levels of IL-17, VEGF and ß2-MG in serum of progress period were higher than those in stable phase and control group, level of IL-35 in serum of control group was significantly higher than that in the stable phase and progress period group (P<0.05). The correlation analysis showed that the level of serum IL-17 positively correlated with VEGF, ß2-MG expression (r=0.65, 0.58, P<0.05); and the serum IL-17 levels were negatively correlated with IL-35 levels (r=-0.42, P<0.05). CONCLUSION: The anomalous levels of IL-17, IL-35, IVEGF and ß2-MG expressions correlate with the progression and prognosis of patients with multiple myeloma.

Clinical Values of Combined Diffused Optical Tomography and PET-CT in the Diagnosis of Breast Cancer.

Objective To investigate the clinical values of combined diffused optical tomography (DOT) combined positron emission tomography-computed tomography (PET-CT) in the diagnosis of breast cancer. Methods We performed DOT and PET-CT examinations in 38 patients with 40 lesions and compared these images with the pathological results to analyze the sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of these two techniques and their combination.Results The sensitivity,specificity,accuracy,positive predictive value,and negative predictive value in diagnosing breast cancer were 78.26%,76.47%,77.50%,72.22%,and 81.81% for DOT,86.96%,82.35%,85.00%,86.96%,and 82.35% for PET-CT,and 86.96%,94.12%,90.00%,95.23%,and 84.21% for the combination of PET-CT and DOT.Conclusions DOT and PET-CT are both effective diagnostic methods for breast cancer.Combined DOT and PET-CT can improve the diagnostic efficacy in terms of specificity,positive predictive value,and accuracy.

Familial Gigantiform Cementoma on 99mTc MDP Bone Scintigraphy.

A 14-year-old girl underwent a Tc MDP bone scan to evaluate multiple fractures. The images showed not only expected increased activity at the fracture sites of lower extremities but also intense activity in both sides of the maxilla and mandible. Microscopic examination of the mandible was consistent with a diagnosis of gigantiform cementoma.

Integrin Imaging with 99mTc-3PRGD2 SPECT/CT Shows High Specificity in the Diagnosis of Lymph Node Metastasis from Non-Small Cell Lung Cancer.

Purpose To evaluate an integrin imaging approach based on single photon emission computed tomography (SPECT)/computed tomography (CT) by using technetium 99m (99mTc)-dimeric cyclic arginine-glycine-aspartic acid (RGD) peptides with three polyethylene glycol spacers (3PRGD2) as the tracer to target the integrin αvß3 expression in lung cancer and lymph node metastasis. Materials and Methods With ethics committee approval and written informed consent, 65 patients (41 male, 24 female; mean age, 60 years ± 11 [standard deviation]) with suspicious lung lesions were recruited with informed consent. The patients underwent both 99mTc-3PRGD2 SPECT/CT and fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT within 1 week. Finally, 65 lung lesions in 53 patients were pathologically diagnosed as non-small cell lung cancer (NSCLC) and 14 lung lesions in 12 patients were benign. Per-region analysis of lymph nodes included 248 regions with metastasis and 56 negative regions. Twenty specimens from the removed lung lesions or lymph nodes were stained with integrin αvß3, CD34, and Ki-67 to correlate with the image findings. Receiver operating characteristic curve, z statistics, McNemar test, and χ2 analysis were used to compare the diagnostic performance of the two imaging methods. Results 99mTc-3PRGD2 SPECT/CT was found to be more specific than 18F-FDG PET/CT in the per-region diagnosis of lymph node metastasis (specificity, 94.6% vs 75.0%; P = .008) when the sensitivity of the two methods was comparable (88.3% vs 90.7%; P = .557). There was no significant difference between the two methods in the per-lesion diagnosis of lung tumor (z = 0.82, P = .410). The accumulation level of 99mTc-3PRGD2 was found in positive correlation with the integrin αvß3 expression (r = 0.84, P = .001) and microvessel density (r = 0.63, P = .011) in the tumors. Conclusion 99mTc-3PRGD2 SPECT/CT shows high specificity in the diagnosis of lymph node metastasis from NSCLC, which may benefit surgical decision making for the patients. © RSNA, 2016.

IV Leiomyomatosis on FDG PET/CT.

A 48-year-old woman presented with a 2-month history of right lower extremity edema. Clinical examination only showed right lower limb swelling. Routine laboratory examination revealed no abnormal results. Abdominal ultrasonography identified uterine leiomyoma and soft tissue masses. An abdominal CT demonstrated a continuous mass extending from the right internal and external iliac vein into the common iliac vein and inferior vena cava. To distinguish the mass from malignancy, the patient underwent PET/CT scan which showed increased FDG activity in the mass. However, histopathological examination proved the mass to be IV leiomyomatosis.

99mTc-HYNIC-TOC imaging in the evaluation of pancreatic masses which are potential neuroendocrine tumors.

PURPOSE: The aim of this investigation was to determine the accuracy of the findings and the diagnoses of Tc-hydrazinonicotinyl-Tyr3-octreotide scan (Tc-HYNIC-TOC imaging) in patients with pancreatic masses which were potential neuroendocrine tumors. METHODS: Records of total 20 patients with pancreatic masses were retrospectively reviewed. All of the patients had been revealed by abdominal contrast CT and possibility of neuroendocrine tumors could not be excluded by CT imaging before Tc-HYNIC-TOC imaging. Tc-HYNIC-TOC imaging was performed at 1 and 4 hours post-tracer injection, and SPECT/CT images of the abdomen were also acquired. The image findings were compared to final diagnoses which were made from pathological examination. RESULTS: Among all 20 pancreatic masses evaluated, there were 16 malignant lesions which included 1 ductal adenocarcinoma and 15 neuroendocrine tumors. Tc-HYNIC-TOC imaging identified 14 of 15 pancreatic neuroendocrine tumors and excluded 4 of 5 lesions which were not neuroendocrine tumors. The overall sensitivity, specificity, and accuracy was therefore 93.3% (14 of 15), 80% (4 of 5), and 90.0% (18 of 20), respectively, in our patient population. CONCLUSION: Tc-HYNIC-TOC imaging provides reasonable accuracy in the evaluation pancreatic mass suspected to be neuroendocrine tumors.

Comparison of 99mTc-3PRGD2 integrin receptor imaging with 99mTc-MDP bone scan in diagnosis of bone metastasis in patients with lung cancer: a multicenter study.

PURPOSE: 99mTc-3PRGD2, a promising tracer targeting integrin receptor, may serve as a novel tumor-specific agent for single photon emission computed tomography (SPECT). A multi-center study was prospectively designed to evaluate the diagnostic accuracy of 99mTc-3PRGD2 imaging for bone metastasis in patients with lung cancer in comparison with the conventional 99mTc-MDP bone scan. METHODS: The patients underwent whole-body scan and chest tomography successively at both 1 h and 4 h after intravenous injection of 11.1 MBq/Kg 99mTc-3PRGD2. 99mTc-MDP whole-body bone scan was routinely performed within 1 week for comparison. Three experienced nuclear medicine physicians blindly read the 99mTc-3PRGD2 and 99mTc-MDP images. The final diagnosis was established based on the comprehensive assessment of all available data. RESULTS: A total of 44 patients (29 male, 59±10 years old) with suspected lung cancer were recruited from 4 centers. Eighty-nine bone lesions in 18 patients were diagnosed as metastases and 23 bone lesions in 9 patients were benign. In a lesion-based analysis, 99mTc-3PRGD2 imaging demonstrated a sensitivity, specificity, and accuracy of 92.1%, 91.3%, and 92.0%, respectively. The corresponding diagnostic values for 99mTc-MDP bone scan were 87.6%, 60.9%, and 82.1%, respectively in the same patients. 99mTc-MDP bone scan had better contrast in most lesions, whereas the 99mTc-3PRGD2 imaging seemed to be more effective to exclude pseudo-positive lesions and detect bone metastases without osteogenesis. CONCLUSION: 99mTc-3PRGD2 is a novel tumor-specific agent based on SPECT technology with a promising value in diagnosis of bone metastasis in patients with lung cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT01737112.

Anti-tumor effect of integrin targeted (177)Lu-3PRGD2 and combined therapy with Endostar.

PURPOSE: Targeted radiotherapy (TRT) is an emerging approach for tumor treatment. Previously, 3PRGD2 (a dimeric RGD peptide with 3 PEG4 linkers) has been demonstrated to be of advantage for integrin αvß3 targeting. Given the promising results of (99m)Tc-3PRGD2 for lung cancer detection in human beings, we are encouraged to investigate the radiotherapeutic efficacy of radiolabeled 3PRGD2. The goal of this study was to investigate and optimize the integrin αvß3 mediated therapeutic effect of (177)Lu-3PRGD2 in the animal model. EXPERIMENTAL DESIGN: Biodistribution, gamma imaging and maximum tolerated dose (MTD) studies of (177)Lu-3PRGD2 were performed. The targeted radiotherapy (TRT) with single dose and repeated doses as well as the combined therapy of TRT and the anti-angiogenic therapy (AAT) with Endostar were conducted in U87MG tumor model. The hematoxylin and eosin (H&E) staining and immunochemistry (IHC) were performed post-treatment to evaluate the therapeutic effect. RESULTS: The U87MG tumor uptake of (177)Lu-3PRGD2 was relatively high (6.03 ± 0.65 %ID/g, 4.62 ± 1.44 %ID/g, 3.55 ± 1.08 %ID/g, and 1.22 ± 0.18 %ID/g at 1 h, 4 h, 24 h, and 72 h postinjection, respectively), and the gamma imaging could visualize the tumors clearly. The MTD of (177)Lu-3PRGD2 in nude mice (>111 MBq) was twice to that of (90)Y-3PRGD2 (55.5 MBq). U87MG tumor growth was significantly delayed by (177)Lu-3PRGD2 TRT. Significantly increased anti-tumor effects were observed in the two doses or combined treatment groups. CONCLUSION: The two-dose TRT and combined therapy with Endostar potently enhanced the tumor growth inhibition, but the former does not need to inject daily for weeks, avoiding a lot of unnecessary inconvenience and suffering for patients, which could potentially be rapidly translated into clinical practice in the future.