TY - JOUR

T1 - uPAR PET/CT for Prognostication and Response Assessment in Patients with Metastatic Castration-Resistant Prostate Cancer Undergoing Radium-223 Therapy

T2 - A Prospective Phase II Study

AU - Fosbol, Marie Obro

AU - Mortensen, Jann

AU - Petersen, Peter Meidahl

AU - Loft, Annika

AU - Madsen, Jacob

AU - Kjaer, Andreas

PY - 2021

Y1 - 2021

N2 - The aim of this Phase II study was to investigate the potential for response assessment and prognostication of positron emission tomography (PET) using the ligand Ga-68-NOTA-AE105 targeting the urokinase-type plasminogen activator receptor (uPAR) in patients receiving Radium-223-dichloride therapy ((RaCl2)-Ra-223). A combined whole-body uPAR PET and computed tomography (CT) was performed before initiation of (RaCl2)-Ra-223 and after two cycles of therapy. Standardized uptake value (SUV) in selected bone metastases was measured and the lesion with the highest SUVmax was considered the index lesion. Clinical outcomes were overall survival (OS), radiographic progression free survival (rPFS) and occurrence of symptomatic skeletal event (SSE). A total of 17 patients were included and 14 patients completed both baseline and follow-up uPAR-PET/CT. Baseline SUVmax of the index lesion was associated with OS; hazard ratio 2.51 (95% CI: 1.01-6.28, p = 0.05) per unit increase in SUVmax. No association between changes in SUVmax from baseline to follow-up and OS, progression during therapy, or rPFS was found. Baseline SUVmax was a significant predictor of SSE with receiver operating characteristics (ROC) area under the curve (AUC) = 0.81 (95% CI: 0.58-1.00, p = 0.034). A cut-off for tumor SUVmax could be established with an odds ratio of 14.0 (95% CI: 1.14-172.6, p = 0.023) for occurrence of SSE within 12 months. Although based on a small number of patients, uPAR-PET SUVmax in bone metastases was predictive for OS and risk of SSE in mCRPC patients receiving (RaCl2)-Ra-223. However, a relatively low uptake of the uPAR ligand in bone metastases impedes visual evaluation and requires another modality for lesion delineation.

AB - The aim of this Phase II study was to investigate the potential for response assessment and prognostication of positron emission tomography (PET) using the ligand Ga-68-NOTA-AE105 targeting the urokinase-type plasminogen activator receptor (uPAR) in patients receiving Radium-223-dichloride therapy ((RaCl2)-Ra-223). A combined whole-body uPAR PET and computed tomography (CT) was performed before initiation of (RaCl2)-Ra-223 and after two cycles of therapy. Standardized uptake value (SUV) in selected bone metastases was measured and the lesion with the highest SUVmax was considered the index lesion. Clinical outcomes were overall survival (OS), radiographic progression free survival (rPFS) and occurrence of symptomatic skeletal event (SSE). A total of 17 patients were included and 14 patients completed both baseline and follow-up uPAR-PET/CT. Baseline SUVmax of the index lesion was associated with OS; hazard ratio 2.51 (95% CI: 1.01-6.28, p = 0.05) per unit increase in SUVmax. No association between changes in SUVmax from baseline to follow-up and OS, progression during therapy, or rPFS was found. Baseline SUVmax was a significant predictor of SSE with receiver operating characteristics (ROC) area under the curve (AUC) = 0.81 (95% CI: 0.58-1.00, p = 0.034). A cut-off for tumor SUVmax could be established with an odds ratio of 14.0 (95% CI: 1.14-172.6, p = 0.023) for occurrence of SSE within 12 months. Although based on a small number of patients, uPAR-PET SUVmax in bone metastases was predictive for OS and risk of SSE in mCRPC patients receiving (RaCl2)-Ra-223. However, a relatively low uptake of the uPAR ligand in bone metastases impedes visual evaluation and requires another modality for lesion delineation.

KW - urokinase-type plasminogen activator receptor (uPAR)

KW - prostate cancer

KW - PET

KW - Radium-223 therapy

KW - PLASMINOGEN-ACTIVATOR RECEPTOR

KW - IN-VITRO

KW - CONTRIBUTES

KW - EXPRESSION

KW - PEPTIDE

KW - DISEASE

KW - SYSTEM

KW - GROWTH

U2 - 10.3390/diagnostics11061087

DO - 10.3390/diagnostics11061087

M3 - Journal article

C2 - 34198666

VL - 11

JO - Diagnostics

JF - Diagnostics

SN - 2075-4418

IS - 6

M1 - 1087

ER -