Preclinical Evaluation of 68Ga-Labeled SL1 Aptamer for c-Met Targeted PET Imaging.

Abstract

Tyrosine protein kinase c-Met, encoded by the Met gene, is a membrane-associated receptor tyrosine kinase that is often aberrantly expressed in a wide range of tumors. The development of imaging probes specifically targeting c-Met is critical for improving cancer diagnostics. In this study, we successfully designed and fabricated an aptamer molecular imaging probe ([⁶⁸Ga]Ga-NOTA-SL1) with high radiochemical purity (RCP), good stability in vitro, and high affinity for c-Met expressed tumors. As shown by the micro-PET/CT scanning, [⁶⁸Ga]Ga-NOTA-SL1 efficiently imaged tumor models with varying c-Met expression. The quantitative analysis of micro-PET/CT showed tumor uptake of [⁶⁸Ga]Ga-NOTA-SL1 in the HCC827 tumor models (30 min, 2.93 ± 0.64%ID/g; 60 min, 2.03 ± 0.67%ID/g; 90 min, 1.63 ± 0.61%ID/g), PC-9 tumor models (30 min, 2.1 ± 0.72%ID/g; 60 min, 1.7 ± 0.56%ID/g; 90 min, 1.33 ± 0.38%ID/g), and HCT116 tumor models (30 min, 1.4 ± 0.17%ID/g; 60 min, 1.23 ± 0.15%ID/g; 90 min, 0.97 ± 0.21%ID/g). The results of immunohistochemistry (IHC) further confirmed the targeting ability of [⁶⁸Ga]Ga-NOTA-SL1 to c-Met from a molecular pathological perspective. The probe effectively imaged c-Met-positive tumors and demonstrated a favorable metabolism profile and targeting performance in non-small cell lung cancer (NSCLC) or colorectal cancer tumor models. Consequently, this probe shows promise as an imaging agent capable of providing valuable diagnostic insights into tumors with aberrant c-Met expression.