Vimentin-targeted radiopeptide 99mTc-HYNIC-(tricine/EDDA)-VNTANST: a promising drug for pulmonary fibrosis imaging

Abstract

Objective Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by the accumulation of extracellular matrix. Because there is no effective treatment for advanced IPF to date, its early diagnosis can be critical. Vimentin is a cytoplasmic intermediate filament that is significantly up-regulated at the surface of fibrotic foci with a crucial role in fibrotic morphological changes. Methods In the present study, VNTANST sequence as a known vimentin-targeting peptide was conjugated to hydrazinonicotinic acid (HYNIC) and labeled with 99mTc. The stability test in saline and human plasma and log P determination were performed. Next, the biodistribution study and single photon emission computed tomography (SPECT) integrated with computed tomography (CT) scanning were performed in healthy and bleomycin-induced fibrosis mice models. Results The 99mTc-HYNIC-(tricine/EDDA)-VNTANST showed a hydrophilic nature (log P = −2.20 ± 0.38) and high radiochemical purity > 97% and specific activity (336 Ci/mmol). The radiopeptide was approximately 93% and 86% intact in saline and human plasma within 6 h, respectively. The radiopeptide was substantially accumulated in the pulmonary fibrotic lesions (test vs. control = 4.08 ± 0.08% injected dose per gram (ID/g) vs. 0.36 ± 0.01% ID/g at 90 min postinjection). SPECT-CT images in fibrosis-bearing mice also indicated the fibrotic foci and kidneys. Conclusion Because there is no available drug for the treatment of advanced pulmonary fibrosis, early diagnosis is the only chance. The 99mTc-HYNIC-(tricine/EDDA)-VNTANST could be a potential tracer for SPECT imaging of pulmonary fibrosis.