PET-Trackable Carborane-Conjugated Star-Shaped Poly(2-Oxazoline) Scaffold with High Boron Payload and Improved Aqueous Solubility for Potential Application in Boron Neutron Capture Therapy

High Resolution Image Download MS PowerPoint Slide Boron neutron capture therapy (BNCT) requires high, tumor-selective boron delivery, yet carboranes, boron-rich BNCT building blocks, often suffer from poor aqueous solubility and suboptimal in vivo behavior despite exceptional boron density and stability. We report a modular star-shaped poly(2-oxazoline) (POx) scaffold that carries a high carborane payload and can be followed by positron emission tomography (PET). An alkyne-bearing POx was conjugated with azidopropyl meta -carborane, yielding PBMM- m CB 20 -EIP that remained highly water-soluble (225 g/L, ∼26 g/L of boron, 20 carboranes/star). PBMM- m CB 20 -EIP exhibited good cytocompatibility in CAL 27 and FaDu head-and-neck cancer cells and showed higher cell-associated boron concentration than the clinical agent sodium borocaptate. A DOTA-modified analogue was prepared and radiolabeled with gallium-68 for PET imaging. In healthy mice, gallium-68-labeled DOTA-PBMM- m CB 20 revealed substantial blood-pool activity (17%ID/g) at 90 min, predominant renal clearance, and low background uptake, providing a baseline for further macromolecular engineering of this carrier and irradiation-timing optimization in tumor models.