Development of Theranostic (177)Lu-Labeled Polymeric Nanoparticles ((177)Lu-PNPs) for the Treatment of Head and Neck Cancer.

This study presents the development of (177)Lu-labeled polymeric nanoparticles (PNPs) for theranostic applications in head and neck cancer, utilizing both near-infrared II (NIR-II) and SPECT imaging for targeted delivery and monitoring. The PNPs were surface-modified with ethylenediamine and chelated with DTPA to enable (177)Lu radiolabeling, achieving a radiochemical yield of 15.4% ± 3.2% and high purity (>95%). The radiolabeling process preserved the size distribution and optical properties of PNPs, facilitating their use in NIR-II imaging, which confirmed effective tumor delivery with peak uptake at 24 h postinjection. Photothermal therapy (PTT) combined with (177)Lu-PNPs significantly enhanced tumor uptake and therapeutic efficacy, as shown by tumor growth suppression and extended survival in treated mice. Importantly, mice receiving the (177)Lu-PNPs-PTT combination therapy exhibited minimal toxicity, as indicated by stable body weight and unaltered organ histology on H&E staining. These findings demonstrate the potential of (177)Lu-PNPs as a safe and effective multifunctional platform for imaging-guided photothermal-radionuclide cancer therapy.