Vimentin-targeted radiopeptide 99m Tc-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 99m Tc. 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 99m Tc-HYNIC-(tricine/EDDA)-VNTANST showed a hydrophilic nature (log P  = -2.20 ±â€…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 ±â€…0.08% injected dose per gram (ID/g) vs. 0.36 ±â€…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 99m Tc-HYNIC-(tricine/EDDA)-VNTANST could be a potential tracer for SPECT imaging of pulmonary fibrosis.