Biological evaluation of integrin α 3 β 1 -targeted 68 Ga-labeled HEVNPs in HCT 116 colorectal tumor-bearing mice

• Published in: European journal of pharmaceutical sciences 2023-01, Vol.180, p.106336
• Main Authors: Lambidis, Elisavet, Chen, Chun-Chieh, Lumen, Dave, Sánchez, Ana Isabel Fraguas, Sarparanta, Mirkka, Cheng, R Holland, Airaksinen, Anu J
• Format: Article
• Language: English
• Subjects: Animals; Colorectal Neoplasms - diagnostic imaging; Gallium Radioisotopes; HCT116 Cells; Humans; Integrin alpha3beta1 - metabolism; Mice; Peptides - chemistry; Positron-Emission Tomography - methods; Radiopharmaceuticals - chemistry
• ISSN: 1879-0720
• DOI: 10.1016/j.ejps.2022.106336

Integrins are cell surface receptors involved in multiple functions vital for cellular proliferation. Various tumor cells overexpress αβ-integrins, making them ideal biomarkers for diagnostic imaging and tumor-targeted drug delivery. LXY30 is a peptide that can specifically recognize and interact with the integrin α β , a molecule overexpressed in breast, ovarian and colorectal cancer. Hepatitis E virus nanoparticles (HEVNPs) are virus-like particles that have been investigated as drug delivery agents for the targeted delivery of nucleic acids and small proteins. HEVNPs can be a theranostic platform for monitoring and evaluating tumor-targeted therapies if tagged with a suitable diagnostic marker. Herein, we describe the radiolabeling and biological evaluation of integrin α β -targeted HEVNPs. HEVNPs were conjugated with DOTA and radiolabeled with gallium-68 (t  = 67.7 min), a short-lived positron emitter used in positron emission tomography (PET). The synthesized [ Ga]Ga-DOTA-HEVNPs were used to evaluate the efficacy of conjugated LXY30 peptide to improve HEVNPs binding and internalization to integrin α β expressing human colorectal HCT 116 cells. In vivo tumor accumulation of [ Ga]Ga-DOTA-HEVNP-LXY30 was evaluated in HCT 116 colorectal tumor-bearing mice. [ Ga]Ga-DOTA-HEVNP-LXY30 and non-targeted [ Ga]Ga-DOTA-HEVNP were radiolabeled with radiochemical yields (RCY) of 67.9 ± 3.3% and 73.7 ± 9.8%, respectively. [ Ga]Ga-DOTA-HEVNP-LXY30 exhibited significantly higher internalization in HCT 116 cells than the non-targeted [ Ga]Ga-DOTA-HEVNPs (21.0 ± 0.7% vs. 10.5 ± 0.3% at 3 h, ***P