Tc-99m and Fluorescence-Labeled Anti-Flt1 Peptide as a Multimodal Tumor Imaging Agent Targeting Vascular Endothelial Growth Factor-Receptor 1

다국어 초록 (Multilingual Abstract)

Purpose We developed a Tc-99m and fluorescence-labeled peptide, Tc-99m TAMRA-GHEG-ECG-GNQWFI, to target tumorcells, and evaluated the diagnostic performance as a dual-modality imaging agent for tumor in a murine model.
Methods TAMRA-GHEG-ECG-GNQWFI was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling ofTAMRA-GHEG-ECG-GNQWFI with Tc-99m was done using ligand exchange via tartrate. Binding affinity and in vitrocellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies wereperformed in murine models with U87MG tumors. Tumor tissue slides were prepared and analyzed with immunohistochemistryusing confocal microscopy.
Results After radiolabeling procedures with Tc-99m, Tc-99m TAMRA-GHEG-ECG-GNQWFI complexes were prepared inhigh yield (> 95%). The Kd of Tc-99m TAMRA-GHEG-ECG-GNQWFI determined by saturation binding was 29.5 ± 4.5 nM.
Confocal microscopy images of U87MG cells incubated with TAMRA-GHEG-ECG-GNQWFI showed strong fluorescence inthe cytoplasm. Gamma camera imaging revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-GNQWFI in tumors.
Tumor uptake was effectively blocked by the co-injection of an excess concentration of GNQWFI. Specific uptake of Tc-99mTAMRA-GHEG-ECG-GNQWFI was assessed by biodistribution, ex vivo imaging, and immunohistochemistry stain studies.
Conclusions In vivo and in vitro studies revealed substantial and specific uptake of Tc-99m TAMRA-GHEG-ECG-GNQWFI intumor cells. Tc-99m TAMRA-GHEG-ECG-GNQWFI could be a good candidate dual-modality imaging agent for tumors.

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