European Urology Oncology Prospective Study of the Radiolabeled GRPR Antagonist BAY86-7548 for Positron Emission Tomography/Computed Tomography Imaging of Newly Diagnosed Prostate Cancer  Karim A. Touijer, Laure Michaud, Herbert A. Vargas Alvarez, Anuradha Gopalan, Susanne Kossatz, Mithat Gonen, Bradley Beattie, Israel Sandler, Serge Lyaschenko, James A. Eastham, Peter T. Scardino, Hedvig Hricak, Wolfgang A. Weber  European Urology Oncology  DOI: 10.1016/j.euo.2018.08.011 Copyright © 2018 Terms and Conditions

Fig. 1 Maximum standardized uptake (SUVmax) of the dominant lesion according to Gleason score. European Urology Oncology DOI: (10.1016/j.euo.2018.08.011) Copyright © 2018 Terms and Conditions

Fig. 2 Receiver operating characteristic curves for each imaging modality and maximum standardized uptake (SUV) of 68Ga-RM2 on PET. PET=positron emission tomography; MRI=magnetic resonance imaging. European Urology Oncology DOI: (10.1016/j.euo.2018.08.011) Copyright © 2018 Terms and Conditions

Fig. 3 Maximum standardized uptake (SUVmax) of normal prostate tissue (PT), benign prostatic hyperplasia (BPH) and dominant tumor. European Urology Oncology DOI: (10.1016/j.euo.2018.08.011) Copyright © 2018 Terms and Conditions

Fig. 4 Lymph node metastasis on pathology correctly diagnosed by 68Ga-RM2 PET and missed by mpMRI. The patient was 61 yr of age and had prostate-specific antigen of 9.1ng/ml. (A) 68Ga-RM2 PET/CT maximum intensity projection image showing the physiologic distribution of 68Ga RM2. (B) Transverse 68Ga-RM2 PET/CT fusion image reveals a lesion (maximum standardized uptake 21.9) involving all of the prostate, predominant on the left side, with potential extracapsular extension. (C) Transverse T2-weighted MRI and (D) apparent diffusion coefficient map revealing the same lesion with a low signal. (E) Histopathology section shows the lesion has a Gleason score of 9 (4+5). (F) Transverse 68Ga-RM2 PET/CT fusion image shows high focal uptake in a left internal iliac lymph node highly suspicious of metastasis (confirmed on histology). (G) On transverse T1-weighted MRI, the left internal iliac lymph node does not appear enlarged and is considered nonsuspicious (false-negative lymph node). PET=positron emission tomography; mpMRI=multiparametric magnetic resonance imaging; CT=computed tomography. European Urology Oncology DOI: (10.1016/j.euo.2018.08.011) Copyright © 2018 Terms and Conditions

Fig. 5 Lymph node metastasis on pathology correctly diagnosed by mpMRI and missed by 68Ga-RM2 PET. The patient was 56 yr of age and had prostate-specific antigen of 1.4ng/ml. (A) 68Ga-RM2 PET/CT maximum intensity projection image showing the physiologic distribution of 68Ga RM2. (B) Transverse 68Ga-RM2 PET/CT fusion image reveals very low uptake (maximum standardized uptake 1.5) in the left mid-gland posterior, considered equivocal evidence of cancer. Of note, the avid area near the pubic bone is due to urine at the bladder neck. (C) Transverse T2-weighted and (D) apparent diffusion coefficient MRI show a low-signal lesion in the left posterior peripheral zone, consistent with prostate cancer. (E) Histopathology section shows the lesion has a Gleason score of 7 (4+3). (F) Transverse 68Ga-RM2 PET/CT fusion image reveals no uptake in an enlarged right internal iliac lymph node, considered negative for metastasis by 68Ga-RM2 PET. (G) Transverse T1-weighted MRI shows that the lymph node is enlarged and thus suspicious for metastasis (confirmed on histology). PET=positron emission tomography; mpMRI=multiparametric magnetic resonance imaging; CT=computed tomography. European Urology Oncology DOI: (10.1016/j.euo.2018.08.011) Copyright © 2018 Terms and Conditions

Fig. 6 Relationship between immunohistochemistry (IHC) staining scores for prostate-specific membrane antigen (PSMA) and GRPR. European Urology Oncology DOI: (10.1016/j.euo.2018.08.011) Copyright © 2018 Terms and Conditions

Fig. 7 Tumor negative for prostate-specific membrane antigen (PSMA). The patient had prostate-specific antigen of 4.3ng/ml and a Gleason score of 7 (3+4). (A) Hematoxylin and eosin section revealing tumor on the left. (B) IHC for PSMA at (B1) low magnification and (B2) 20× magnification; score=0.3. (C) Transverse 68Ga-RM2 PET/CT fusion image shows high tumoral uptake (maximum standardized uptake 11.3) in posterior lesions involving both sides of the prostate, predominant in the left, evocative of prostate cancer. (D) IHC for GRPr; (D1) low magnification, (D2) 20x magnification; score=2.6. IHC=immunohistochemistry; PET=positron emission tomography; mpMRI=multiparametric magnetic resonance imaging; CT=computed tomography. European Urology Oncology DOI: (10.1016/j.euo.2018.08.011) Copyright © 2018 Terms and Conditions

Fig. 8 Tumor negative for GRPR. The patient had prostate-specific antigen of 9.7ng/ml and a Gleason score of 7 (3+4). (A) Hematoxylin and eosin section shows tumor on the right. (B) IHC for PSMA at (B1) low magnification and (B2) 20× magnification; score=2.5. (C) Transverse 68Ga-RM2 PET/CT fusion image shows moderate tumoral uptake (maximum standardized uptake 4.5) in the center of the prostate evocative of prostate cancer. (D) IHC for GRPR at (D1) low magnification and (D2) 20× magnification; score=1.4. IHC=immunohistochemistry; PET=positron emission tomography; mpMRI=multiparametric magnetic resonance imaging; CT=computed tomography. European Urology Oncology DOI: (10.1016/j.euo.2018.08.011) Copyright © 2018 Terms and Conditions