Targeting of MMP2 activity in malignant tumors with a 68Ga-labeled gelatinase inhibitor cyclic peptide

Nuclear Medicine and Biology
Qinghua LiuChangjing Zuo

Abstract

Elevated levels of gelatinases (matrix metalloproteinases 2/9, i.e., MMP2 and MMP9) are associated with tumor progression, invasion and metastasis, so these enzymes are potential targets for tumor imaging. The peptide c(KAHWGFTLD)NH2 (herein, C6) is a selective gelatinase inhibitor. Cy5.5-C6 has been visualized in many tumor models in vivo. However, the sensitivity and penetrance of optical imaging are poor. It is well known that positron emission tomography (PET) has a high detection sensitivity and Gallium-68 ((68)Ga) is an optimal PET radioisotope. Thus, in the present study, we developed a novel ligand, (68)Ga-NOTA-C6, to image MMP2 activity in tumors. C6 was conjugated with the bifunctional chelator NOTA (1,4,7-triazacyclononanetriacetic acid) and labeled with (68)Ga. In vitro uptake and binding analyses were performed by using SKOV3 cell lines, coincubating with or without the MMP inhibitor doxycycline. The biodistribution and PET imaging were conducted on SKOV3 ovarian tumor models. MMP2 expression in tumors was analyzed by immunohistochemistry (IHC). The non-decay corrected yield of (68)Ga-NOTA-C6 was 61.8%-63.3%. (68)Ga-NOTA-C6 was stable in both physiological saline and human serum. The uptake of (68)Ga-NOTA-C6 in SKO...Continue Reading

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Citations

Aug 29, 2017·International Journal of Molecular Sciences·Artor Niccoli AsabellaGiuseppe Rubini
Sep 21, 2017·Molecular Imaging·Brian P RempelChristopher P Phenix
Oct 11, 2019·Biomolecules & Therapeutics·Joon-Seok Choi, Sang Hoon Joo
May 1, 2021·Pharmaceutics·Abiodun Ayo, Pirjo Laakkonen
May 10, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Katarzyna StaszakKrzysztof Roszkowski
Jun 3, 2021·International Journal of Molecular Sciences·Alexandru FloreaMatthias Bauwens

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