EGFR targeting of [177Lu] gold nanoparticles to colorectal and breast tumour cells: Affinity, duration of binding and growth inhibition of Cetuximab-resistant cells

Radioimmunotherapy (RIT) is a systemic therapy currently used in the treatment of patients with lymphoma. RIT complexes consist targeting molecule, commonly an antibody, radionuclide chelates and linker which can be nanoparticle platform. Nanoparticles facilitate attachment multiple radionuclides groups to single complex. Here target affinity, duration association inhibition colony formation Cetuximab-resistant tumour cells Cetuximab-targeted [177Lu]-AuNPs were investigated. Dose distribution xenografts derived from EGFR-overexpressing was also determined. generated by functionalising 15nm AuNPs chelator DOTA Cetuximab radiolabelling 177LuCl3. KDis, measure determined competitive binding EGFR expressing cells. Radio-sensitivity including resistant cell line HCT116 using assay. measured sections grown nude mice autoradiography. KDis for complex on MDA-MB-468 20 nM. Loss associated [177Lu] activity biphasic loss about 50% 4 h. Remaining dissociated over period days. HCT8 MDA-MB-468, but not sensitive growth inhibitory effect Cetuximab. However, inhibited all 3 lines. across found demonstrate co-efficient variation 15%. high affinity could effective colorectal cancer A strategy involving pre-treatment receptor targeted[177Lu] improve therapeutic ratios has potential enhance clinical outcomes.