Abstract P5-01-04: uPAR PET imaging in breast cancer: First-in-humans studies using 64Cu-DOTA-AE105 and 68Ga-NOTA-AE105
Authors: Kjaer A , Persson M , Skovgaard D , Brandt-Larsen M , Christensen C , Madsen J , Nielsen CH , Loft A , Berthelsen AK , Kroman N , Højgaard L 
Published: May 2016

Abstract
Objective
The urokinase-type plasminogen activator receptor (uPAR) is a well-established prognostic biomarker in many cancer types including breast cancer (BC). Numerous studies using immunohistochemically evaluation of uPAR expression in tissue samples from BC patients have shown that not only is uPAR consistently overexpressed, but also carries strong prognostic value and is associates with overall survival. Accordingly, uPAR is an obvious target for identifying BC and for phenotyping aggressiveness in BC. Using whole body Positron Emission Tomography (PET) imaging rather than tissue specimens circumvents possible sampling error and allows for staging. Our objective was therefore to perform first-in-humans studies of uPAR-specific PET imaging in BC using either 64Cu-DOTA-AE105 or 68Ga-NOTA-AE105
Methods
Six patients with BC and scheduled for surgery were included. Prior to operation, patients were either PET/CT scanned 1, 3 and 24 h after injection of the uPAR PET ligand 64Cu-DOTA-AE105 (n=3; half life of 64Cu: 13 h) or PET/CT scanned 10 min, 1 h or 2 h after injection of 68Ga-NOTA-AE105 (n=3; half life of 68Ga: 1 h). PET Images were visually analyzed for visible tumor uptake of 64Cu-DOTA-AE105 or 68Ga-NOTA-AE105 and Standardized Uptake Values (SUV) were obtained by manually drawing volumes of interest (VOIs) around the primary tumor as well as identified metastases. Results are given as SUVmax. Tumor-to-background ratios relative to liver, kidney, blood and muscle were also calculated. Surgical tumor specimens were obtained from all patients during subsequent surgery. In addition to routine pathological examination, tissue was analyzed for ex vivo uPAR expression as target validation.
Results
Both primary tumors and metastases were visually detectable. For 64Cu-DOTA-AE105 SUVmax values were 2.9–4.0., and 2.9-4.0 after 1 and 3 h, respectively. Tumor-to-background ratios after 1 h were 0.91 (tumor-liver), 1.65 (tumor-kidney), 0.96 (tumor-blood) and 8.9 (tumor-muscle), respectively. Tumor-to-background ratios after 3 h were 0.50 (tumor-liver), 0.96 (tumor-kidney), 4.2 (tumor-blood) and 11.4 (tumor-muscle), respectively. Ex vivo analysis by immunohistochemistry confirmed uPAR expression in all primary cancer lesions. For 68Ga-NOTA-AE105, SUVmax was 5.0, 3.8 and 4.2 after 10 min, 1 h and 3 h, respectively (first patient analyzed). Tumor-to-background ratios after 10 min were 2.8 (tumor-liver), 0.4 (tumor-kidney), 1.6 (tumor-blood) and 8.4 (tumor-muscle), respectively. Tumor-to-background ratios after 1 h were 3.2 (tumor-liver), 0.6 (tumor-kidney), 1.7 (tumor-blood) and 7.1 (tumor-muscle), respectively.
Conclusion
This is the first study in humans using PET imaging of uPAR in BC. Both primary tumors and metastases were clearly visible with robust PET tracer uptake and a high and sufficient contrast between tumors and background. Our data supports continuation into phase II clinical studies using uPAR PET for staging and risk stratification, which potentially may be used for selection of treatment strategy in BC.
Citation Format: Kjaer A, Persson M, Skovgaard D, Brandt-Larsen M, Christensen C, Madsen J, Nielsen CH, Loft A, Berthelsen AK, Kroman N, Højgaard L. uPAR PET imaging in breast cancer: First-in-humans studies using 64Cu-DOTA-AE105 and 68Ga-NOTA-AE105. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-01-04.