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

Bioconjugate Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 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.

Language: Английский

Selective PET imaging of CXCR4 using the Al18F-labeled antagonist LY2510924

European Journal of Nuclear Medicine and Molecular Imaging, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

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^99mTc-Labeled D-Type PTP as a Plectin-Targeting Single-Photon Emission Computed Tomography Probe for Hepatocellular Carcinoma Imaging

Bioconjugate Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 21, 2024

Plectin, a scaffolding protein overexpressed in tumor cells, plays significant role hepatocellular carcinoma (HCC) proliferation, invasion, and migration. However, the use of L-type peptides for targeting plectin is hindered by their limited stability retention. We designed D-type plectin-targeting peptide (DPTP) developed novel single-photon emission computed tomography (SPECT) probe HCC imaging. The DPTP ability was evaluated vitro using flow cytometry ex vivo fluorescence 99mTc radiolabeling performed tricine ethylenediamine-N,N′-diacetic acid (EDDA) as coligands after modification with 6-hydrazino nicotinamide (HYNIC) at N termini DPTP. radiochemical purity (RCP), stability, binding affinity prepared 99mTc-HYNIC-DPTP were analyzed. Tumor uptake, metabolic biodistribution, pharmacokinetics investigated compared those 99mTc-labeled PTP (99mTc-HYNIC-PTP) tumor-bearing mice. could be efficiently radiolabeled HYNIC/tricine/EDDA system high RCP good stability. Compared PTP, exhibited improved ability, displayed higher better longer blood circulation time, lower kidney retention, resulting superior imaging performance biodistribution vivo. has great potential SPECT diagnosing HCC.

Language: Английский