Synthesis and Evaluation of 99mTc-Labeled Folate-Tripeptide Conjugate as a Folate Receptor-Targeted Imaging Agent in a Tumor-Bearing Mouse Model View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-09

AUTHORS

Myoung Hyoun Kim, Woo Hyoung Kim, Chang Guhn Kim, Dae-Weung Kim

ABSTRACT

PURPOSE: The folate receptor (FR) is an attractive molecular target since it is overexpressed in a variety of human tumors. The purpose of the present study was to synthesize and evaluate the feasibility of a novel (99m)Tc-ECG-EDA (Glu-Cys-Gly-ethylenediamine)-folate as an FR-positive tumor imaging agent in a mouse tumor model. MATERIALS AND METHODS: ECG-EDA-folate was synthesized using solid phase peptide synthesis (SPPS) and radiolabeled with (99m)Tc using tripeptide ECG as a chelator. FR-positive KB cells were inoculated in athymic nude mice. Following injection of (99m)Tc-ECG-EDA-folate, serial scintigraphy and micro-SPECT/CT imaging were performed at various time points with and without pre-administration of excess free folate. Mean count densities (MCD) for regions of interest drawn on KB tumors and major normal organs at each time point were measured, and uptake ratios of tumor to normal organs were calculated. RESULTS: ECG-EDA-folate was labeled with (99m)Tc with high radiolabeling efficiency and stability (>96 %). FR-positive tumors were clearly visualized on both scintigraphy and micro-SPECT/CT images and the tumor uptake of (99m)Tc-ECG-EDA-folate was markedly suppressed with faint visualization of tumors by pre-administration of excess free folate on serial planar scintigraphy, indicating FR-specific binding of the agent. Furthermore, semiquantitative analysis of MCD data showed again that both tumor MCD and tumor-to-normal organ ratios decreased considerably by pre-administration of excess free folate, supporting FR-specific tumor uptake. Tumor-to-normal organ ratios approximately increased with time after injection until 4 h. CONCLUSION: The present study demonstrated that (99m)Tc-ECG-EDA-folate can bind specifically to FR with clear visualization of FR-positive tumors in a mouse tumor model. More... »

PAGES

200-207

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s13139-015-0336-2

DOI

http://dx.doi.org/10.1007/s13139-015-0336-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1051948801

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26279693


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