Dual Functionality of [64Cu]Cu-NOTA-San A-Cy7 for Diagnostic Imaging and Surgical Guidance in Hsp90α-Positive Tumors DOI
Zhijun Li, Tukang Peng, Min Yang

et al.

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: May 9, 2025

Intraoperative fluorescence navigation in esophageal cancer enables the clinical translation of imaging. Heat shock protein 90 alpha (Hsp90α) plays a vital role progression malignant disease, and elevated Hsp90α expression has been reported cancer. The aim this study was to develop dual-modality probe, [64Cu]Cu-NOTA-San A-Cy7, for imaging vivo via both positron emission tomography (PET) In study, Hsp90α-targeting cyclopeptide Sansalvamide A (San A) chemically modified with Cy7 dye NOTA chelator simultaneously. Experimental assays confirmed that NOTA-San A-Cy7 favorable affinity Hsp90α-positive EC109 cells, dissociation constant (Kd) 1.08 ± 0.19 μM. probe successfully synthesized 64CuCl2, achieving high radiochemical purity over 95%. Furthermore, demonstrated excellent stability saline serum solutions. subsequently evaluated tumor-bearing model PET imaging, which Hsp90α-specific uptake significantly reduced by co-administration an excess blocking agent. Biodistribution studies revealed at 24 hours post-injection, tumor 1.35 0.29%ID/g nonblocking group decreased 0.73 0.15%ID/g (p < 0.05). Concurrent experiment, conducted, revealing substantial model. As proof concept, imaging-guided surgery utilizing fluorescent component performed. This approach potential providing surgical guidance mice positive Hsp90α, highlighting dual functionality diagnostic intraoperative navigation. summary, our findings unequivocally demonstrate holds significant promise as agent tumors vivo, offering valuable tool detection management such tumors.

Language: Английский

Evaluation of a Novel Gd-FAPI Dimer Molecular Probe Targeting Fibroblast Activation Protein for Imaging of Solid Tumors DOI Creative Commons
Xiaohui Wang, Caiyu Zhuang,

Xinhui Zheng

et al.

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

Cancer-associated fibroblasts (CAFs) are essential components of the tumor microenvironment. Fibroblast activation protein (FAP) is overexpressed in CAFs. FAP-targeted molecular imaging agents, including FAP inhibitors (FAPIs), have shown promising results diagnosis. We aimed to design a Gd-labeled FAPI Dimer, Gd-DOTA-Suc-Lys-(FAPI04)2, optimize pharmacokinetics and evaluate its potential capacity for targeting FAP-positive solid tumors vivo. The Dimer was successfully synthesized with exceeding 98% purity. Preclinical were determined assessed U87 cell-derived xenografts FAP-negative C6-derived using small-animal T1-weighted 7.0T MR imaging. longitudinal correlation coefficient (r1) agent 3.813 mM-1·S-1. administration Gd-FAPI04 probe showed notable enhancement contrast on whole-body MRI. At 10 30 minutes post-injection, subcutaneous demonstrated significantly greater than C6 (P <0.05). In vivo, safety Gd-FAPI-04 evaluated, which no tissue damage vital organs like heart, liver, spleen, lung, kidneys, as indicated by unchanged morphology compared normal saline control group. novel probe, Gd-DOTA-Suc-Lys-(FAPI-04)2 specifically may serve safe tool diagnostic tumors.

Language: Английский

Citations

0
Dual Functionality of [64Cu]Cu-NOTA-San A-Cy7 for Diagnostic Imaging and Surgical Guidance in Hsp90α-Positive Tumors DOI
Zhijun Li, Tukang Peng, Min Yang

et al.

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: May 9, 2025

Intraoperative fluorescence navigation in esophageal cancer enables the clinical translation of imaging. Heat shock protein 90 alpha (Hsp90α) plays a vital role progression malignant disease, and elevated Hsp90α expression has been reported cancer. The aim this study was to develop dual-modality probe, [64Cu]Cu-NOTA-San A-Cy7, for imaging vivo via both positron emission tomography (PET) In study, Hsp90α-targeting cyclopeptide Sansalvamide A (San A) chemically modified with Cy7 dye NOTA chelator simultaneously. Experimental assays confirmed that NOTA-San A-Cy7 favorable affinity Hsp90α-positive EC109 cells, dissociation constant (Kd) 1.08 ± 0.19 μM. probe successfully synthesized 64CuCl2, achieving high radiochemical purity over 95%. Furthermore, demonstrated excellent stability saline serum solutions. subsequently evaluated tumor-bearing model PET imaging, which Hsp90α-specific uptake significantly reduced by co-administration an excess blocking agent. Biodistribution studies revealed at 24 hours post-injection, tumor 1.35 0.29%ID/g nonblocking group decreased 0.73 0.15%ID/g (p < 0.05). Concurrent experiment, conducted, revealing substantial model. As proof concept, imaging-guided surgery utilizing fluorescent component performed. This approach potential providing surgical guidance mice positive Hsp90α, highlighting dual functionality diagnostic intraoperative navigation. summary, our findings unequivocally demonstrate holds significant promise as agent tumors vivo, offering valuable tool detection management such tumors.

Language: Английский

Citations

0