Open Access

ARTICLE

Imaging urothelial bladder cancer: A VPAC PET targeted approach

Mathew L. Thakur^1,2,3,4, Sushil K. Tripathi¹, Leonard G. Gomella^3,4, Ebru Salmanoglu⁵, Sung Kim¹, William K. Kelly^4,6, Scott W. Keith⁷, Charles Intenzo¹, Peter McCue⁸, Jean Hoffman-Censits⁹, Edouard J. Trabulsi^3,4

1 Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
2 Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
3 Department of Urology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
4 Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
5 Department of Nuclear Medicine, Kahramanmaras, Onikisubat, Turkey
6 Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
7 Department of Pharmacology and Experimental Therapeutics, Division of Biostatistics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
8 Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
9 Johns Hopkins Greenberg Bladder Cancer Institute, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, Maryland, USA
Address correspondence to Prof. Mathew L. Thakur, PhD, Thomas Jefferson University, 1020 Locust Street, Suite 359 JAH, Philadelphia, PA 19107 USA

Canadian Journal of Urology 2021, 28(2), 10596-10602.

Abstract

Introduction: Accurate staging of urothelial bladder cancer (UBC) with imaging, which guides effective bladder cancer treatment, remains challenging. This investigation is to validate a hypothesis that targeting vasoactive intestinal and pituitary adenylate cyclase activating peptide (VPAC) receptors using ⁶⁴Cu-TP3805 can PET image UBC efficiently.
Materials and methods: Nineteen patients (aged 44-84 years) scheduled for radical cystectomy underwent VPAC positron emission tomography (PET) imaging prior to surgery. Sixteen had completed neoadjuvant chemotherapy before imaging. All 19 received ⁶⁴Cu-TP3805 (148% ± 10% MBq) intravenously and were imaged 60 to 90 minutes later. Standard uptake value (SUV)max for malignant lesions and SUVmean for normal tissues were determined, and mean ± SEM recorded. Following radical cystoprostatectomy, pelvic lymphadenectomy, and urinary diversion imaging, results were compared with final surgical pathology.
Results: ⁶⁴Cu-TP3805 had no adverse events, negligible urinary excretion, and rapid blood clearance. UBC PET images for residual disease were true positive in 11 patients and true negative in four. Of the remaining four, one had a false positive and three had false negatives, equating to 79% sensitivity (95% CI 49%-95%), 80% specificity (95% CI 28%-100%), 92% positive predictive value (95% CI 62%-100%), and 57% negative predictive value (95% CI 18%-90%).
Conclusions: These first-in-man results, in a group heavily pretreated with neoadjuvant chemotherapy, indicate that VPAC PET imaging can identify UBC efficiently and suggest that VPAC PET can diagnose UBC in a treatment-naive cohort for accurate staging, guide biopsy and treatment in patients with suspected metastasis, and determine response to therapy. Further investigation of this molecular imaging approach is warranted.

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