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18F?alfatide positron emission tomography may predict anti?angiogenic responses
摘要： As the crucial issue in the development of anti-angiogenic drugs is how to predict which patients will and will not benefit prior to the initiation of therapy, angiogenic 18F-alfatide positron emission computed tomography (PET) was assessed in the present study. Lung adenocarcinoma A549 (high angiogenesis) and prostate PC?3 (low angiogenesis) cell xenografted tumor-bearing mice underwent 18F-alfatide PET at baseline and following treatment with either an anti?angiogenic therapy or vehicle. The evaluation index for the inhibition of tumor growth in the individuals in the treated groups was represented by treatment/control (T/C) ratio (%). Anti?angiogenic responses were denoted by the changes in 18F-alfatide uptake in the same animal. The T/C ratio was lower in high-uptake tumors than in low?uptake tumors (P=0.001). A significant difference in the tumor volumes between the anti?angiogenic therapy group and the control group occurred earlier in the A549 model than in the PC?3 model. 18F-alfatide uptake decreased more for A549 tumors than for PC?3 tumors following anti?angiogenic therapy. In each treatment group, the degree of tumor response to anti?angiogenic therapy was associated well with the tumor uptake prior to treatment (P<0.05). These results indicated that 18F?alfatide PET may be a useful molecular imaging tool for individual selection prior to anti?angiogenic drug therapy.
关键词： 18F?alfatide positron emission tomography,heterogeneity,integrin αvβ3,response prediction,anti?angiogenic therapy
更新于2025-09-23 15:22:29
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Integrin α <sub/>γ</sub> β <sub/>3</sub> -targeted [ <sup>64</sup> Cu]CuS Nanoparticles for PET/CT Imaging and Photothermal Ablation Therapy
摘要： Copper sulfide (CuS) nanoparticles have been considered one of the most clinical relevant nanosystems because of their straightforward chemistry, small particle size, low toxicity, and intrinsic theranostic characteristics. In our previous studies, radioactive [64Cu]CuS nanoparticles were successfully developed to be used as efficient radiotracers for positron emission tomography and for photothermal ablation therapy of cancer cells using near-infrared laser irradiation. However, the major challenge of CuS nanoparticles as a theranostic platform is the lack of a means for effective targeted delivery to the tumor site. To overcome this challenge, we designed and synthesized angiogenesis-targeting [64Cu]CuS nanoparticles, which are coupled with cyclic RGDfK peptide [c(RGDfK)] through polyethylene glycol (PEG) linkers using click chemistry. In assessing their tumor-targeting efficacy, we found that the tumor uptakes of [64Cu]CuS-PEG-c(RGDfK) nanoparticles at 24 h after intravenous injection were significantly greater (8.6%±1.4% injected dose/gram of tissue) than those of nontargeted [64Cu]CuS-PEG nanoparticles (4.3%±1.2% injected dose/gram of tissue, p < 0.05). Irradiation of tumors in mice administered [64Cu]CuS-PEG-c(RGDfK) nanoparticles induced 98.7% necrotic areas. In contrast, irradiation of tumors in mice administered non-targeted CuS-PEG nanoparticles induced 59% necrotic areas (p < 0.05). The angiogenesis-targeting [64Cu]CuS nanoparticles may serve as a promising platform for image-guided ablation therapy with high efficacy and minimal side effects in future clinical translation of this novel class of multifunctional nanomaterials.
关键词： PET/CT imaging,RGD peptide,Copper sulfide nanoparticles,photothermal ablation therapy,integrin αvβ3,theranostics
更新于2025-09-23 15:21:21
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[99mTc]3PRGD2 for integrin receptor imaging of esophageal cancer: a comparative study with [18F]FDG PET/CT
摘要： Objectives This study was designed to investigate the efficacy of 99mtechnetium-three polyethylene glycol spacers-arginine–glycine–aspartic acid ([99mTc]3PRGD2) in the evaluation of patients with esophageal cancer. Methods Twenty-nine patients with a suspected esophageal lesion and for whom definite pathological diagnosis was finally obtained were recruited. Whole-body planar scanning and chest single-photon-emission computed tomography/computed tomography (SPECT/CT) were performed at 30 and 40?min, respectively, after intravenous injection of 11.1?MBq/kg of [99mTc]3PRGD2. 2-Deoxy-2-[18F] fluoro-d-glucose ([18F]FDG) positron-emission tomography/computed tomography (PET/CT) was performed in 1?week. The tumor-to-background ratio (T/B) and the maximum standard uptake value (SUVmax) were calculated for semi-quantitative and quantitative analyses. Integrin αvβ3 was analyzed through immunohistochemistry. Results The T/B, SUVmax and expression of integrin αvβ3 in malignant lesions were higher than those in benign lesions (t = 3.691, P = 0.001; t = 8.271, P = 0.000; t = 3.632, P = 0.001, respectively). There was a significant correlation between T/B and SUVmax in esophageal lesions (r = 0.660, P = 0.000). The expression of integrin αvβ3 was correlated with [99mTc]3PRGD2 uptake (r = 0.782, P = 0.000). In visual analysis, the sensitivity and accuracy of the whole-body planar RGD scan were lower than those of the chest SPECT/CT RGD scan and the [18F]FDG PET/CT scan (x2 = 6.769, P = 0.022). The sensitivity, specificity and accuracy of the chest SPECT/CT RGD scan were similar to those of the [18F] FDG PET/CT scan. In semi-quantitative analysis, the sensitivity, specificity and accuracy of chest SPECT/CT RGD from the receiver operating characteristic (ROC) analysis were 87%, 100% and 94%, respectively [cutoff = 3.1 of T/B, area under the curve (AUC) = 0.957]. Thirteen patients (30 lymph nodes) and 16 patients (105 lymph nodes) were suspected to have lymph node metastases based on the RGD and FDG scans, respectively. Conclusion This prospective study demonstrated that [99mTc]3PRGD2 imaging is valuable for the diagnosis and staging of esophageal cancer. It may be less sensitive than [18F]FDG imaging for detecting metastatic lesions in small lymph nodes. The T/B value was correlated with the expression of integrin αvβ3.
关键词： Esophageal cancer,SPECT,[99mTc]3PRGD2,Integrin αvβ3
更新于2025-09-23 15:21:01
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Synthesis and characterization of 64Cu- and Cy5.5-labeled tetraiodothyroacetic acid derivatives for tumor angiogenesis imaging
摘要： It was previously reported that tetraiodothyroacetic acid (tetrac) inhibits angiogenesis by binding to the cell surface receptor for thyroid hormone on integrin αVβ3. Therefore, we synthesized and evaluated two 64Cu-labeled tetrac derivatives and a Cy5.5-labeled tetrac derivative for tumor angiogenesis imaging. Tetrac was structurally modified to conjugate with 1,4,7,10-tetraazacyclododecane-N,N′,N″,N″′-tetraacetic acid (DOTA) via its hydroxy or carboxylic acid end, and the resulting DOTA-conjugated tetrac derivatives were then labeled with 64Cu. Tetrac was also conjugated with Cy5.5 via its carboxylic acid end. All three tetrac derivatives (1–3) exhibited greater inhibitory activity than tetrac against endothelial cell tube formation. The U87MG cell binding of [64Cu]2 showed a time-dependent increase over 24 h and it was inhibited by 38% at 4 h in the presence of tetrac, indicating specificity of [64Cu]2 to the thyroid hormone receptor site on integrin αVβ3. Positron emission tomography (PET) images of U87MG tumor-bearing mice injected with [64Cu]1 and [64Cu]2 revealed that high radioactivity accumulated in the tumors, and that the tumor uptake and tumor-to-nontarget uptake ratio were higher in small tumors than in large tumors. In addition, the Cy5.5-labeled tetrac derivative (3) displayed a strong near-infrared (NIR) signal in the tumors. Taken together, these results suggest that these ligands hold promise as imaging agents for visualization of tumor angiogenesis.
关键词： Near-infrared imaging,Integrin αVβ3,Angiogenesis,Positron emission tomography,Tetraiodothyroacetic acid
更新于2025-09-11 14:15:04