10.3390/polym8030084

Vollständiger Abstract

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<b>Background/Objectives:</b> Because human prostate cancer (PCa) typically exhibits slow tumor growth, establishing reliable PCa tumor models is often time-consuming and unpredictable, thereby limiting the efficiency of preclinical theranostic research. To overcome this limitation, this study employed a non-viral <i>PiggyBac</i> transposon system to introduce triple-reporter genes into PSMA-expressing C4-2 cells, generating orthotopic and subcutaneous xenograft models that allow noninvasive, real-time monitoring of PCa progression and treatment response. <b>Methods:</b> Reporter-engineered C4-2 3R cells were generated by co-transfecting constructs encoding the reporter cassette and PB transposase, followed by enrichment through fluorescence microscopy and fluorescence-activated cell sorting (FACS) and implantation orthotopically or subcutaneously into mice. Tumor growth and treatment response to a single 2 Gy X-ray dose followed by 14.8 MBq of 177 Lu-PSMA-617, or to each monotherapy, were monitored weekly using an IVIS imaging system. Imaging findings were validated by tumor dissection and hematoxylin and eosin (H&E) staining, while PSMA expression was assessed by Western blotting and 18 F-PSMA-1007 PET/CT. <b>Results:</b> C4-2 3R cells stably expressed the triple reporter genes (mRFP, luc2, and HSV1-tk), generating detectable orthotopic bioluminescence within one week and persisting for at least five weeks. In contrast, subcutaneous implantation generated only transient luc2 signals with no tumor formation. X-ray exposure did not increase total PSMA levels but induced the redistribution of PSMA to the cell membrane. Combined external beam radiotherapy (EBRT) and 177 Lu-PSMA-617 treatment produced higher 18 F-PSMA-1007 uptake and stronger tumor suppression, with minimal residual tumor mass, as compared to single-treatment or control groups. <b>Conclusions:</b> This preliminary investigation suggests that the C4-2 3R model provides a practical and trackable tool for investigating slow-growing PCa tumors and evaluating PSMA-targeted therapies, either alone or in combination with EBRT.

Abstract: PubMed · Datensatz