157Gd-DHK: enhancing targeted gadolinium neutron capture for pancreatic adenocarcinoma

Gadolinium-neutron capture therapy (Gd-NCT) employs Gadolinium (Gd) isotopes and thermal neutrons to specifically target and kill cancer at cells level. This study investigates the targeting efficacy of ¹⁵⁷Gd-DOTA-HK (DHK), a novel agent designed for Gd-NCT and MRI. We synthesized ¹⁵⁷Gd-DHK, which combines a Gd-DOTA complex as a neutron capturer and MRI probe with αvβ6 binding peptide (HK) for targeted Pancreas adenocarcinoma (PDAC) therapy. ¹⁵⁷Gd-DHK demonstrated a significantly high binding affinity for BxPC-3 cells. scintigraphy revealed that the optimal time window for Gd-NCT was 26 h after injection. The conjugate's imaging capabilities and its potential as an MRI contrast agent were validated. The conjugate effectively triggered nuclear reactions via Gd-NCT, leading to efficient tumor cell destruction. Photon sensitization studies showed that ¹⁵⁷Gd-DHK induced photon-mediated phototoxicity in cancer cells while exhibiting minimal toxicity. ¹⁵⁷Gd-DHK shows great potential as a theranostic agent for targeted imaging of PDAC and Gd-NCT applications. It presents a novel strategy to enhance the specificity and efficacy of Gd-NCT in cancer treatment.