TY - JOUR
T1 - Imaging Urothelial Bladder Cancer
T2 - A VPAC PET Targeted Approach
AU - Thakur, Mathew L.
AU - Tripathi, Sushil K.
AU - Gomella, Leonard G.
AU - Salmanoglu, Ebru
AU - Kim, Sung
AU - Kelly, William K.
AU - Keith, Scott W.
AU - Intenzo, Charles
AU - McCue, Peter
AU - Hoffman-Censits, Jean
AU - Trabulsi, Edouard J.
N1 - Funding Information:
Funding: Supported in part by NIH, NCI RO1 157372 (MLT), DTSA (MLT) and SKCC (MLT). Conflict of interest: Mathew Thakur, PhD, holds a US patent on the Cu-64-TP3805 PET imaging technology, licensed to NuviewDx. He is consultant to NuviewDX and KOP therapeutics Inc. Leonard Gomella, MD, reports conflicts of interest, the entities are Astellas, Abbvie, Astra Zeneca, Bayer, Ferring, Merck, Clovis and MDx Health: advisory board. Jean Hoffman-Censits, MD reports conflicts of interest, the entities are Genetech, Foundation Medicine: research support, Seattle Genetics: paid advisory board, and Astra Zeneca: paid consultant. Edouard Trabulsi, MD, reports conflicts of interest, the entities are Pfizer, Astellas, Janssen, and GenomeDx: personal fees. All other authors have no conflict of interest to report.
Funding Information:
Acknowledgements The results of this investigation, in part, were presented at the 2019 SNMMI Annual Meeting and were included in the highlights of the meeting by Dr. Andrew Scott. The investigation was supported, in part, by NIH, NCI RO1 157372 (MLT), DTSA (MLT) and SKCC (MLT). The authors thank Mrs. Nancy Pedano, Clinical Research Coordinator and her associates for their outstanding services, the members of the PET/CT imaging technologists and Ms. Kim Lee for their excellent contributions. Dr. Ebru Salmanoglu was a visiting scholar to the Thakur laboratories and thanks The Scientific and Technological Research Council of Turkey (TÜBİTAK) for their fellowship and Dr. Thakur for his teaching and support.
Publisher Copyright:
© The Canadian Journal of Urology™
PY - 2021/4
Y1 - 2021/4
N2 - 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 (44-84 years of age) scheduled for radical cystectomy, underwent VPAC positron emission tomography (PET) imaging prior to surgery. Sixteen had completed neoadjuvant chemotherapy prior to 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 remaining 4, one had false positive and 3 had false negative scans, 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 effeiciently and suggest, that VPAC PET can diagnose UBC in a treatment naïve 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.
AB - 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 (44-84 years of age) scheduled for radical cystectomy, underwent VPAC positron emission tomography (PET) imaging prior to surgery. Sixteen had completed neoadjuvant chemotherapy prior to 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 remaining 4, one had false positive and 3 had false negative scans, 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 effeiciently and suggest, that VPAC PET can diagnose UBC in a treatment naïve 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.
KW - Cu-TP3805
KW - bladder cancer
KW - computed tomography
KW - positron emission tomography
KW - radioisotope diagnostic technique
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M3 - Article
C2 - 33872557
AN - SCOPUS:85105903804
SN - 1195-9479
VL - 28
SP - 10596
EP - 10602
JO - Canadian Journal of Urology
JF - Canadian Journal of Urology
IS - 2
ER -