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

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• 作者：Myoung Hyoun Kim ; Woo Hyoung Kim ; Chang Guhn Kim…
• 关键词：Folate receptor ; Molecular imaging ; Technetium 99m ; SPECT
• 刊名：Nuclear Medicine and Molecular Imaging
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：49
• 期：3
• 页码：200-207
• 全文大小：704 KB
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• 作者单位：Myoung Hyoun Kim (1)
  Woo Hyoung Kim (2)
  Chang Guhn Kim (1) (3)
  Dae-Weung Kim (1) (3)
  
  1. Department of Nuclear Medicine, Wonkwang University School of Medicine, Iksan, Korea
  2. Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea
  3. Institute of Wonkwang Medical Science, Iksan, Korea
  
• 刊物主题：Nuclear Medicine; Imaging / Radiology; Orthopedics; Cardiology; Oncology;
• 出版者：Springer Berlin Heidelberg
• ISSN：1869-3482

文摘

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 99mTc-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 99mTc using tripeptide ECG as a chelator. FR-positive KB cells were inoculated in athymic nude mice. Following injection of 99mTc-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 99mTc 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 99mTc-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 99mTc-ECG-EDA-folate can bind specifically to FR with clear visualization of FR-positive tumors in a mouse tumor model.