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A novel Tc-99m and fluorescence labeled peptide: Multimodal imaging agent for targeting angiogenesis in a murine tumor model

Date

10 Oct 2016

Session

Poster display

Presenters

Dae-Weung Kim

Citation

Annals of Oncology (2016) 27 (6): 401-406. 10.1093/annonc/mdw380

Authors

D. Kim1, S. Kim2, M.H. Kim3, W.H. Kim4, C.G. Kim3

Author affiliations

  • 1 Department Of Nuclear Medicine And Research Unit Of Molecular Imaging Agent (rumia), Wonkwang University Hospital, 570-711 - Iksan/KR
  • 2 Research Unit Of Molecular Imaging Agent (rumia), Wonkwang University Hospital, Iksan/KR
  • 3 Department Of Nuclear Medicine, Wonkwang University Hospital, Iksan/KR
  • 4 Department Of Nuclear Medicine, Chonbuk National University Medical School and Hospital, Jeon Ju/KR
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Resources

Abstract 962

Background

The serine-aspartic acid-valine (SDV) peptide binds specifically to integrin αvß3. In the present study, we successfully developed both Tc-99m and TAMRA labeled TAMRA-GHEG-ECG-SDV peptide to target the integrin αvß3 of tumor cells; furthermore, we evaluated the diagnostic performance of Tc-99m TAMRA-GHEG-ECG-SDV as a dual-modality imaging agent for tumor of the murine model.

Methods

TAMRA-GHEG-ECG-SDV synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling of TAMRA-GHEG-ECG-SDV with Tc-99m was done using ligand exchange methods. Labeling stability and cytotoxicity studies were performed. Gamma camera imaging, biodistribution and ex vivo imaging studies were performed in murine models with HT-1080 and HT-29 tumors. Tumor tissue slide was prepared and analyzed using confocal microscopy.

Results

After radiolabeling procedures with Tc-99m, the Tc-99m TAMRA-GHEG-ECG-SDV complexes were prepared in high yield (>99%). Tc-99m TAMRA-GHEG-ECG-SDV was found to be nontoxic to HUVEC and HT-1080 cells at all concentration. On gamma camera imaging study, a substantial uptake of Tc-99m TAMRA-GHEG-ECG-SDV into HT-1080 tumor (integrin αvß3-positive) and low uptake of Tc-99m TAMRA-GHEG-ECG-SDV in HT-29 tumor (integrin αvß3-negative) were demonstrated. The HT-1080 tumor-to-normal muscle uptake ratio of Tc-99m TAMRA-GHEG-ECG-SDV reached 6.8 ± 2.3 at 3 h (2.8 ± 0.7, 5.3 ± 1.5 and 6.8 ± 2.3 at 1, 2 and 3 h, respectively). The HT-29 tumor-to-normal muscle uptake ratios of Tc-99m TAMRA-GHEG-ECG-SDV (1.6 ± 0.4, 1.7 ± 0.4 and 2.0 ± 0.5 at 1, 2 and 3 h, respectively) were significantly lower than those of HT-1080 tumor (p 

Conclusions

Our in vivo and in vitro studies revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-SDV on the integrin αvß3-positive tumor. Tc-99m TAMRA-GHEG-ECG-SDV could be a good candidate for dual-modality imaging agent targeting tumor angiogenesis.

Clinical trial identification

N/A

Legal entity responsible for the study

Wonkwang University School of Medicine

Funding

This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2013R1A1A2059262).

Disclosure

All authors have declared no conflicts of interest.

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