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CT imaging in prostate cancer: A first-in-humans study
Title
932
UPAR PET/CT imaging in prostate cancer: A first-in-humans study Eur Urol Suppl 2015;14/2;e932
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Persson M. 1 , Skovgaard D.1 , Madsen J. 1 , Nielsen C.H.1 , Loft A. 1 , Brandt-Larsen M. 1 , Christensen C.1 , Hoejgaard L. 1 , Brasso K. 2 , Kjaer A. 1 1 Rigshospitalet,
Dept. of Clinical Physiology, Nuclear Medicine and Pet and Cluster For Molecular Imaging, University of Copenhagen,
Copenhagen, Denmark, 2 Rigshospitalet, Dept. of Urology, Copenhagen, Denmark INTRODUCTION & OBJECTIVES: Numerous studies have demonstrated the urokinase-type plasminogen activator receptor (uPAR) to be of special importance in cancer invasion and metastatic potential, also in prostate cancer (PC). Thorough studies by immuno-histochemistry and in situ hybridization have revealed low expression levels of uPAR in normal prostate tissue compared with prostate cancer. Furthermore, plasma levels of uPAR have been associated with advanced PC stage and bone metastasis. High preoperative plasma uPAR levels have been shown to correlate with early progression. Because of uPAR’s important role in PC molecular biology, uPAR is an attractive target for molecular imaging with PET. Our aim was therefore to perform the first proof-of-concept PET imaging study of uPAR in PC patients. MATERIAL & METHODS: Four patients with newly diagnosed localized prostate cancer, with a PSA level ranging from 7.7 to 150 and a Gleason score of 7 (n=1) or 9 (n=3), were enrolled in the study. Each patient had a uPAR PET/CT scan performed after 1, 3 and 24 hrs post injection of the uPAR PET ligand 64 Cu-DOTA-AE105. Primary endpoints were safety and biodistribution. Secondary endpoints were tumour uptake and tumour-to-background ratio analysis. RESULTS: No safety issues following the uPAR PET imaging procedure were found in any patients. A fast clearance of the PET ligand was observed in vivo, generating a high contrast already after 1 hr post injection. In all four PC patients, high and specific uptake in the tumour lesions were found, with SUVmax values of 9.6±2.1, 9.9±2.3 and 3.3±0.8 after 1, 3 and 24 hr, respectively. One hour post injection, a tumour-to-liver, tumour-to-kidney, tumour-to-muscle and tumour-to-blood ratios of 0.7, 0.8, 4.5 and 1.6 were found, respectively. CONCLUSIONS: We developed an uPAR PET ligand and performed the first-in-humans study in PC patients. The high and specific tumour uptake is encouraging and we suggest the method could be used as a non-invasive tool for risk stratification and early detection of aggressive disease in patients with localized PC. Further studies are needed to prove the validity of such a concept.
file:///S|/IM/EURSUP/2015%20EAU%20Abstracts/content/data/932.html[19/02/2015 08:23:41]
932
UPAR PET/CT imaging in prostate cancer: A first-in-humans study Eur Urol Suppl 2015;14/2;e932
Print! Print!
Persson M. 1 , Skovgaard D.1 , Madsen J. 1 , Nielsen C.H.1 , Loft A. 1 , Brandt-Larsen M. 1 , Christensen C.1 , Hoejgaard L. 1 , Brasso K. 2 , Kjaer A. 1 1 Rigshospitalet,
Dept. of Clinical Physiology, Nuclear Medicine and Pet and Cluster For Molecular Imaging, University of Copenhagen,
Copenhagen, Denmark, 2 Rigshospitalet, Dept. of Urology, Copenhagen, Denmark INTRODUCTION & OBJECTIVES: Numerous studies have demonstrated the urokinase-type plasminogen activator receptor (uPAR) to be of special importance in cancer invasion and metastatic potential, also in prostate cancer (PC). Thorough studies by immuno-histochemistry and in situ hybridization have revealed low expression levels of uPAR in normal prostate tissue compared with prostate cancer. Furthermore, plasma levels of uPAR have been associated with advanced PC stage and bone metastasis. High preoperative plasma uPAR levels have been shown to correlate with early progression. Because of uPAR’s important role in PC molecular biology, uPAR is an attractive target for molecular imaging with PET. Our aim was therefore to perform the first proof-of-concept PET imaging study of uPAR in PC patients. MATERIAL & METHODS: Four patients with newly diagnosed localized prostate cancer, with a PSA level ranging from 7.7 to 150 and a Gleason score of 7 (n=1) or 9 (n=3), were enrolled in the study. Each patient had a uPAR PET/CT scan performed after 1, 3 and 24 hrs post injection of the uPAR PET ligand 64 Cu-DOTA-AE105. Primary endpoints were safety and biodistribution. Secondary endpoints were tumour uptake and tumour-to-background ratio analysis. RESULTS: No safety issues following the uPAR PET imaging procedure were found in any patients. A fast clearance of the PET ligand was observed in vivo, generating a high contrast already after 1 hr post injection. In all four PC patients, high and specific uptake in the tumour lesions were found, with SUVmax values of 9.6±2.1, 9.9±2.3 and 3.3±0.8 after 1, 3 and 24 hr, respectively. One hour post injection, a tumour-to-liver, tumour-to-kidney, tumour-to-muscle and tumour-to-blood ratios of 0.7, 0.8, 4.5 and 1.6 were found, respectively. CONCLUSIONS: We developed an uPAR PET ligand and performed the first-in-humans study in PC patients. The high and specific tumour uptake is encouraging and we suggest the method could be used as a non-invasive tool for risk stratification and early detection of aggressive disease in patients with localized PC. Further studies are needed to prove the validity of such a concept.
file:///S|/IM/EURSUP/2015%20EAU%20Abstracts/content/data/932.html[19/02/2015 08:23:41]