Selection of the optimal chelator for labeling of DARPin Ec1 with gallium-68 for PET imaging of EpCAM expression DOI Creative Commons
Anzhelika Vorobyeva,

M. I. Din,

Alexey Schulga

и другие.

EJNMMI Radiopharmacy and Chemistry, Год журнала: 2025, Номер 10(1)

Опубликована: Май 30, 2025

Abstract Background Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein, which overexpressed in several types of malignancies. Designed ankyrin repeat protein (DARPin) Ec1 19 kDa engineered scaffold that binds with high affinity to EpCAM. Radiolabelled might be used as companion diagnostic for the selection patients personalized therapy. This study aimed investigate influence different radiometal-chelator complexes on biodistribution and imaging contrast 68 Ga-labelled Ec1. To this, two macrocyclic chelators, 1,4,7-triazacyclononane-N,N,N-triacetic acid (NOTA) 1-(1,3-carboxypropyl)-1,4,7-triazacyclononane-4,7-diacetic (NODAGA) were conjugated C-terminus The previously developed DARPin 1,4,7,10-tetraazacylododecane-1,4,7,10-tetraacetic (DOTA) was comparator. Results All variants successfully labelled Ga. use NOTA NODAGA provided twice higher radiochemical yield improved label stability compared DOTA. bound EpCAM-expressing cells nanomolar preserved targeting specificity vitro vivo. Biodistribution studies mice bearing SKOV-3 xenografts showed [ Ga]Ga-Ec1-NOTA had lower uptake most normal organs while maintaining tumor uptake. Among all variants, lowest liver uptake, no significant differences Additionally, highest tumor-to-blood ratio Ga]Ga-Ec1-DOTA Ga]Ga-Ec1-NODAGA. Conclusion preferred radioconjugate PET EpCAM expression.

Язык: Английский

Dual-Functional Nanobody Optical Probes for In Vivo Fluorescence Imaging and Photodynamic Therapy DOI

Yiqi Zeng,

Siyu Zhou, Yicheng Yang

и другие.

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Фев. 14, 2025

Nanobodies have gained significant attention as promising tools for cancer diagnostics and treatment due to their unique ability precisely target specific cells. However, a major challenge lies in the site-specific incorporation of multifunctional molecules into nanobodies, it is essential link these manner that preserves nanobody's function stability while retaining desired therapeutic or diagnostic properties. This study outlines development dual-functional nanobody optical probes enhanced interventions. We designed clickable linker enables functionalization nanobody, facilitating simultaneous conjugation two dyes: indocyanine green imaging chlorin e6 photodynamic therapy. In vitro cellular assays confirmed successful labeling dyes, with probe exhibiting high binding specificity. vivo mice bearing Hep3B tumors revealed clear visualization signal-to-noise ratio. Furthermore, PEGylated significantly improved tumor retention, enhancing both contrast therapy efficacy compared free e6. These show great promise precise diagnosis malignant tumors.

Язык: Английский

Процитировано

0
Indium-111-Labeled Single-Domain Antibody for In Vivo CXCR4 Imaging Using Single-Photon Emission Computed Tomography DOI

M. SPAHN,

Stephanie Mareike Anbuhl,

Kaat Luyten

и другие.

Bioconjugate Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 11, 2025

C-X-C chemokine receptor type 4 (CXCR4) is highly expressed in a range of pathologies, including cancers like multiple myeloma and non-Hodgkin lymphoma, inflammatory diseases such as rheumatoid arthritis, viral infections HIV. Currently, the most advanced radiotracer for CXCR4 imaging clinics [68Ga]PentixaFor. However, its structure prone to modifications, complicating development specific fluorine-18-labeled tracer with good pharmacokinetic properties. This study aimed screen CXCR4-targeting variable domains heavy-chain-only antibody (VHH or single-domain (sdAb)) constructs identify promising sdAb vector molecule future fluorine-18 tracer. We have generated five CXCR4-specific cysteine-containing C-terminal tag (C-Direct tag) (VUN400-C-Direct, VUN401-C-Direct, VUN410-C-Direct, VUN411-C-Direct, VUN415-C-Direct) one probe (VUN400-C) without. The reduced sdAbs were coupled maleimide-DOTAGA 111In-labeling. Their binding affinity against human (hCXCR4) was assessed by using previously described BRET-based displacement assay. vivo profile naive mice. Based on plasma stability (60 min post injection (p.i.)), we selected VUN400-C-Direct derivative VUN400-C further evaluation. These compounds ([111In]In-DOTAGA-VUN400-C-Direct [111In]In-DOTAGA-VUN400-C) tested mice bearing xenografts derived from U87.CD4, U87.CXCR4, U87.CD4.CXCR4 cells through ex biodistribution studies SPECT/CT imaging. six labeled high radiochemical conversion (75–97%) purity (>95%). In radioactive assays cells, [111In]In-DOTAGA-VUN400-C-Direct [111In]In-DOTAGA-VUN401-C-Direct displayed highest cellular uptake, achieving 10.4 ± 1.6% 11.5 1.1%, respectively. mice, showed favorable profile, low uptake across all organs except kidneys (Standardized Uptake Value (SUV) > 50, n = 3, 60 p.i.), but average (40.6 9.4%, p.i.). xenografted tumor model, only minor (SUVU87.CXCR4 0.71 0.002, [111In]In-DOTAGA-VUN400-C demonstrated nearly identical (41.08 5.45%, 4) CXCR4-expressing (SUVU87.CD4.CXCR4 3.75 1.08 vs SUVU87.CD4 0.64 0.19, 5, which could be blocked coinjection AMD3100 (5 mg/kg) 0.55 0.32 0.39 0.07, 2, conclusion, exhibited vitro hCXCR4. Among these, properties, indicating VUN400-C's potential PET applications fluorine-18.

Язык: Английский

Процитировано

0
Development of [18F]AlF-RESCA-H006 as a Novel Molecular Probe for 5T4 Tumor Imaging and Exploration of Its Application in Pancreatic Adenocarcinoma DOI

Jinping Kong,

Huixia Zhang,

Ruhua Tian

и другие.

Molecular Pharmaceutics, Год журнала: 2025, Номер unknown

Опубликована: Май 30, 2025

Pancreatic adenocarcinoma (PAAD) is an extremely lethal cancer, making early detection and precise staging essential for extending survival. Upregulation of 5T4 mRNA was detected in bioinformatics analysis using data from the Cancer Genome Atlas Genotype-Tissue Expression. In current work, we confirmed overexpression protein tumor samples PAAD compared with corresponding paraneoplastic tissue. To visualize via positron emission tomography (PET) noninvasively, successfully developed [18F]AlF-RESCA-H006 based on a single-domain antibody fragment. The radiotracer demonstrated high binding affinity toward antigens vitro remained stable final formulation up to 4 h storage at room temperature. two preclinical mouse models pancreatic clearly identified sites, showing radioactivity accumulation 2.43 ± 0.46% ID/g Balb/C mice BxPC-3 xenografts 2.88 1.02% NCG PANC-1 xenografts. Taken together, promising PET tracer detecting antigen alteration PAAD. Further investigations are required assess its defluorination level higher species permeability through dense extracellular matrix cancer.

Язык: Английский

Процитировано

0
Selection of the optimal chelator for labeling of DARPin Ec1 with gallium-68 for PET imaging of EpCAM expression DOI Creative Commons
Anzhelika Vorobyeva,

M. I. Din,

Alexey Schulga

и другие.

EJNMMI Radiopharmacy and Chemistry, Год журнала: 2025, Номер 10(1)

Опубликована: Май 30, 2025

Abstract Background Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein, which overexpressed in several types of malignancies. Designed ankyrin repeat protein (DARPin) Ec1 19 kDa engineered scaffold that binds with high affinity to EpCAM. Radiolabelled might be used as companion diagnostic for the selection patients personalized therapy. This study aimed investigate influence different radiometal-chelator complexes on biodistribution and imaging contrast 68 Ga-labelled Ec1. To this, two macrocyclic chelators, 1,4,7-triazacyclononane-N,N,N-triacetic acid (NOTA) 1-(1,3-carboxypropyl)-1,4,7-triazacyclononane-4,7-diacetic (NODAGA) were conjugated C-terminus The previously developed DARPin 1,4,7,10-tetraazacylododecane-1,4,7,10-tetraacetic (DOTA) was comparator. Results All variants successfully labelled Ga. use NOTA NODAGA provided twice higher radiochemical yield improved label stability compared DOTA. bound EpCAM-expressing cells nanomolar preserved targeting specificity vitro vivo. Biodistribution studies mice bearing SKOV-3 xenografts showed [ Ga]Ga-Ec1-NOTA had lower uptake most normal organs while maintaining tumor uptake. Among all variants, lowest liver uptake, no significant differences Additionally, highest tumor-to-blood ratio Ga]Ga-Ec1-DOTA Ga]Ga-Ec1-NODAGA. Conclusion preferred radioconjugate PET EpCAM expression.

Язык: Английский

Процитировано

0