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Annals of Nuclear Medicine

, Volume 30, Issue 5, pp 369–379 | Cite as

Preclinical evaluation of isostructural Tc-99m- and Re-188-folate-Gly-Gly-Cys-Glu for folate receptor-positive tumor targeting

  • Woo Hyoung Kim
  • Chang Guhn KimEmail author
  • Myoung Hyoun Kim
  • Dae-Weung Kim
  • Cho Rong Park
  • Ji Yong Park
  • Yun-Sang Lee
  • Hyewon Youn
  • Keon Wook Kang
  • Jae Min Jeong
  • June-Key Chung
Original Article

Abstract

Objective

The purpose of the present study was to prepare isostructural Tc-99m- and Re-188-folate-Gly-Gly-Cys-Glu (folate-GGCE), and to evaluate the feasibility of their use for folate receptor (FR)-targeted molecular imaging and as theranostic agents in a mouse tumor model.

Methods

Folate-GGCE was synthesized using solid-phase peptide synthesis and radiolabeled with Tc-99m or Re-188. Radiochemical characterization was performed by radio-high-performance liquid chromatography. The biodistribution of Tc-99m-folate-GGCE was studied, with or without co-injection of excess free folate, in mice bearing both FR-positive (KB cell) and FR-negative (HT1080 cell) tumors. Biodistribution of Re-188-folate-GGCE was studied in mice bearing KB tumors. Serial planar scintigraphy was performed in the dual tumor mouse model after intravenous injection of Tc-99m-folate-GGCE. Serial micro-single photon emission computed tomography/computed tomography (SPECT/CT) studies were performed, with or without co-injection of excess free folate, in the mouse tumor model after injection of Tc-99m-folate-GGCE or Re-188-folate-GGCE.

Results

The radiolabeling efficiency and radiochemical stability of Tc-99m- and Re-188-folate-GGCE were more than 95 % for up to 4 h after radiolabeling. Uptake of Tc-99m-folate-GGCE at 1, 2, and 4 h after injection in KB tumor was 16.4, 23.2, and 17.6 % injected dose per gram (%ID/g), respectively. This uptake was suppressed by 97.4 % when excess free folate was co-administered. Tumor:normal organ ratios at 4 h for blood, liver, lung, muscle, and kidney were 54.3, 25.2, 38.3, 97.8, and 0.3, respectively. Tumor uptake of Re-188-folate-GGCE at 2, 4, 8, and 16 h after injection was 17.4, 21.7, 24.1, and 15.6 %ID/g, respectively. Tumor:normal organ ratios at 8 h for blood, liver, lung, muscle, and kidney were 126.8, 21.9, 54.8, 80.3, and 0.4, respectively. KB tumors were clearly visualized at a high intensity using serial scintigraphy and micro-SPECT/CT in mice injected with Tc-99m- or Re-188-folate-GGCE. The tumor uptake of these molecules was completely suppressed when excess free folate was co-administered.

Conclusion

Isostructural Tc-99m- and Re-188-folate-GGCE showed high and FR-specific uptake by tumors and generally favorable tumor:normal organ ratios. The tumor targeting capabilities of Tc-99m- and Re-188-folate-GGCE were clearly evident on serial imaging studies. This isostructural pair may have potential diagnostic and theranostic applications for FR-positive tumors.

Keywords

Folate receptor Tumor Tc-99m Re-188 SPECT/CT 

Notes

Acknowledgments

This study was supported by Wonkwang University in 2014.

Compliance with ethical standards

Conflict of interest

No potential conflicts of interest were disclosed.

Supplementary material

12149_2016_1072_MOESM1_ESM.tif (668 kb)
Supplementary material 1 (TIFF 668 kb)

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Copyright information

© The Japanese Society of Nuclear Medicine 2016

Authors and Affiliations

  • Woo Hyoung Kim
    • 1
    • 2
  • Chang Guhn Kim
    • 2
    Email author
  • Myoung Hyoun Kim
    • 2
  • Dae-Weung Kim
    • 2
  • Cho Rong Park
    • 3
  • Ji Yong Park
    • 3
  • Yun-Sang Lee
    • 3
    • 4
  • Hyewon Youn
    • 3
    • 5
    • 6
    • 7
  • Keon Wook Kang
    • 1
    • 3
    • 5
    • 8
  • Jae Min Jeong
    • 3
  • June-Key Chung
    • 3
    • 5
    • 6
    • 8
  1. 1.Department of Nuclear MedicineSeoul National University HospitalSeoulRepublic of Korea
  2. 2.Department of Nuclear Medicine, Institute of Wonkwang Medical ScienceWonkwang University School of MedicineIksanRepublic of Korea
  3. 3.Department of Nuclear MedicineSeoul National University College of MedicineSeoulRepublic of Korea
  4. 4.Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of PharmacySeoul National UniversitySeoulRepublic of Korea
  5. 5.Cancer Research InstituteSeoul National University College of MedicineSeoulRepublic of Korea
  6. 6.Tumor Microenvironment Global Core Research CenterSeoul National UniversitySeoulRepublic of Korea
  7. 7.Cancer Imaging CenterSeoul National University HospitalSeoulRepublic of Korea
  8. 8.Department of Biomedical SciencesSeoul National University College of MedicineSeoulRepublic of Korea

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