Prospective Study of the Radiolabeled GRPR Antagonist BAY86-7548 for Positron Emission Tomography/Computed Tomography Imaging of Newly Diagnosed Prostate Cancer.

Abstract

BACKGROUND:

Current imaging techniques may not detect all prostate cancer (PCa) lesions.

OBJECTIVE:

To evaluate positron emission tomography (PET)/computed tomography (CT) using the radiolabeled GRPR antagonist probe BAY86-7548 (68Ga-RM2) for localization of newly diagnosed PCa in comparison with multiparametric magnetic resonance imaging (mpMRI), histopathology, and immunohistochemistry (IHC).

DESIGN, SETTING, AND PARTICIPANTS:

This was a prospective study of 16 men with biopsy-proven PCa (2 low, 8 intermediate, and 6 high risk). 68Ga-RM2 PET/CT was performed within 4 wk after mpMRI and within 2 wk before radical prostatectomy and extended bilateral pelvic lymph node dissection.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

The presence of cancer was evaluated by blinded specialists using a 5-point Likert scale, with lesions scoring 4 or 5 considered positive, on 68Ga-RM2 PET/CT, mpMRI, and 68Ga-RM2 PET/CT-mpMRI fused images for each of 12 anatomic areas of the prostate. Whole-mount, step-section pathology served as the reference standard. Expression of GRPR and prostate-specific membrane antigen (PSMA) was analyzed via IHC of tumor paraffin sections.

RESULTS AND LIMITATIONS:

Of 192 areas analyzed, 128 contained cancer. The sensitivity, specificity, and accuracy of 68Ga-RM2 PET/CT imaging and mpMRI did not differ significantly; fusing the images maximized the sensitivity and accuracy (85.2% and 83.9%, respectively) and averaged the specificity (81.3%). The area under the receiver operating characteristic curve was 0.76 for PET visual analysis, 0.72 for PET quantitative analysis, 0.76 for mpMRI, and 0.85 for combined PET/CT and mpMRI analysis. 68Ga-RM2 uptake did not correlate with Gleason score. IHC analysis revealed weaker staining for GRPR than for PSMA, and the expression of these markers was not correlated (r=0.3882). The major limitation is the small sample size.

CONCLUSIONS:

68Ga-RM2 PET/CT is promising for detection and localization of primary PCa, and complements mpMRI. GRPR expression appears to be independent from PSMA expression, suggesting that GRPR- and PSMA-targeted PET imaging may be complementary.

PATIENT SUMMARY:

This pilot prospective study shows that a positron emission tomography probe that binds to a marker of prostate cancer, GRPR, improves the ability of magnetic resonance imaging to detect prostate cancer.

• Authors: 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
• Journal: European urology oncology (Eur Urol Oncol) Vol. 2 Issue 2 Pg. 166-173 (03 2019) ISSN: 2588-9311 [Electronic] Netherlands
• PMID: 31017093 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2018. Published by Elsevier B.V.

Chemical References

• Antigens, Surface
• BAY 86-7548
• Oligopeptides
• Receptors, Bombesin
• FOLH1 protein, human
• Glutamate Carboxypeptidase II

Topics

• Aged
• Antigens, Surface (metabolism)
• Glutamate Carboxypeptidase II (metabolism)
• Humans
• Lymph Node Excision
• Male
• Middle Aged
• Multiparametric Magnetic Resonance Imaging (methods)
• Oligopeptides (administration & dosage)
• Pilot Projects
• Positron Emission Tomography Computed Tomography (methods)
• Prospective Studies
• Prostatectomy
• Prostatic Neoplasms (diagnostic imaging, metabolism, surgery)
• Receptors, Bombesin (metabolism)
• Sensitivity and Specificity
• Treatment Outcome