A PET probe targeting polyamine transport system for precise tumor diagnosis and therapy

Polyamine metabolism dysregulation is a hallmark of many cancers,offering a promising avenue for early tumor theranostics.This study presents the development of a nuclear probe derived from spermidine(SPM)for dual-purpose tumor PET imaging and internal radiation therapy.The probe,radiolabeled with either[68Ga]Ga for diagnostic applications or[177Lu]Lu for therapeutic use,was synthesized with exceptional purity,stability,and specific activity.Extensive testing involving 12 different tumor cell lines revealed remarkable specificity towards B16 melanoma cells,showcasing outstanding tumor localization and target-to-non-target ratio.Mechanistic investigations employing polyamines,non-labeled precursor,and polyamine transport system(PTS)inhibitor,consistently affirmed the probe?s targetability through recognition of the PTS.Notably,while previous reports indicated PTS upregulation in various tumor types for targeted therapy,this study observed no positive signals,highlighting a concentration-dependent discrepancy between targeting for therapy and diagnosis.Furthermore,when labeled with[177Lu],the probe demonstrated its therapeutic potential by effectively controlling tumor growth and extending mouse survival.Investigations into biodistribution,excretion,and biosafety in healthy humans laid a robust foundation for clinical translation.This study introduces a versatile SPM-based nuclear probe with applications in precise tumor theranostics,offering promising prospects for clinical implementation.

Nd-doped structurally disordered YSr_(3)(PO_(4))_(3) single crystal:Growth and laser performances

Disordered-structure crystals have drawn increasing attention as promising ultrashort laser material hosts owing to their broad linewidth.Herein,a novel disordered Nd:YSr_(3)(PO_(4))_(3)(Nd:YSP)crystal with good quality was successfully grown via the Czochralski pulling technique.The absorption and fluorescence spectra of the Nd:YSP single crystal were recorded at ambient temperature.The maximum absorption cross section for Nd:YSP single crystal is found to be approximately 3.89×10^(-20) cm^(2).The stimulated emission cross section for Nd:YSP crystal at~1060 nm was determined to be 7.64×10^(20) cm^(2) with the full width half maximum value of 22 nm.The fluorescence lifetime of the Nd3+ions in the Nd:YSP crystal is fitted to be 288μs.Diode-pumped continuous-wave laser operation is firstly realized at approximately 1060 nm.The maximum output power value from the Nd:YSP crystal is 714 mW,corresponding to a slope efficiency of-12.8%.The results indicate that the Nd:YSP crystal with a disordered structure may be a promising disordered laser host.