| dc.description.abstract | Prostate cancer is the most common malignancy diagnosed in men, with the 5-year survival rate significantly declining from over 99% in localized stages to 30% upon progression to metastatic disease. The management of metastatic castration-resistant prostate cancer (mCRPC) is particularly challenging as conventional androgen deprivation therapies become ineffective. Pluvicto (177Lu-vipivotide tetraxetan), a promising targeted radioligand therapy, has recently been approved by the Food and Drug Administration (FDA) for treating prostate-specific membrane antigen (PSMA)-positive mCRPC. In this study, we collected whole blood samples from mCRPC patients throughout their Pluvicto treatment course and investigated systemic and molecular changes in circulating tumor cell (CTC) populations over time. We developed a MATLAB image processing algorithm to batch process the analysis and characterization of patient CTCs. A significant reduction in CTC PSMA expression and diameter was observed across all patients throughout their treatment, underscoring Pluvicto’s ability to effectively target high PSMA expressing cells. Moreover, this decrease in PSMA expression was irrespective of patient therapeutic response and did not always correlate with traditional biomarkers of disease progression. This observation suggests that surviving CTCs may inherently express lower PSMA levels, thereby evading Pluvicto’s targeting mechanism, or they may adapt to the therapeutic pressure imposed by Pluvicto and downregulate PSMA as a survival mechanism. Additionally, trends between prostate-specific antigen (PSA) serum levels and CTC counts generally paralleled therapeutic efficacy, especially in patients demonstrating regressive or stable disease. Overall, this study offers insights into the potential of using CTC characterization and PSMA expression as predictive and monitoring tools for assessing the therapeutic efficacy of Pluvicto treatment in patients with advanced mCRPC. Future research into the molecular changes in mCRPC patient CTCs may enable improved patient outcomes through more personalized and adaptive treatment strategies. | |
