A novel compound used with positron emission tomography imaging can identify foci of prostate cancer not found on biopsy of the prostate pre surgery or on the post-surgery specimen, according to a pilot study presented at the American Association of Cancer Research annual meeting in Philadelphia.
Philadelphia-A novel compound used with positron emission tomography imaging can identify foci of prostate cancer not found on biopsy of the prostate pre surgery or on the post-surgery specimen, according to a pilot study presented at the American Association of Cancer Research annual meeting in Philadelphia.
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The technique utilizes TP3805, a Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase Activating Peptide Receptor 1 (VPAC1)–specific biomolecule labeled with Cu-64 when imaging patients with prostate cancer.
Dr. Trabulsi“VPAC1, a cell surface receptor, is over-expressed in prostate cancer and is a highly suitable target for imaging and treatment. VPAC1 is nonspecific and also upregulated in a variety of tumors,” said presenting author Edouard Trabulsi, MD, associate professor of urology at Kimmel Cancer Center at Thomas Jefferson University, Philadelphia.
The study builds on the work of Mathew Thakur, PhD, also of the Kimmel Cancer Center. Supported by the National Institutes of Health, Dr. Thakur and colleagues studied PET imaging with vasoactive intestinal peptide and VPAC1 in breast and lung cancer and found that it was “exquisitely sensitive” in identifying undiagnosed lesions, Dr. Trabulsi explained.
The first-in-human pilot study presented at AACR 2015 is the first to evaluate this technique in prostate cancer. The study included 25 men diagnosed with prostate cancer slated for radical prostatectomy imaged preoperatively with PET imaging targeting VPAC1. All men underwent conventional biopsy and surgery. The preoperative scans were compared with pathology of the surgical and biopsy specimens.
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Cu-TP305 imaging identified 66% more lesions than prostate biopsy histology and 30% more lesions than whole mount radical prostatectomy histology.
Malignant lesions were those with standardized uptake values >100. A total of 212 lesions were deemed malignant compared with 127 identified by histology.
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prostate cancer foci were identified by PET with VPAC1 in 98% of cases. Two lesions were missed due to technical artifact. Additionally, nine small cancerous lesions were identified on imaging that were not identified on examination of the biopsy slides. A total of 19 additional lesions seen on PET in areas without prostate cancer foci identified areas of high-grade prostatic intraepithelial neoplasia. A positive lymph node and a benign lymph node were correctly identified by PET targeted to VPAC1.
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The positive predictive value of the PET VPAC1-targeted imaging was 97% and the negative predictive value was 100%.
“The study validated VPAC1 as a potential target for prostate cancer and treatment,” Dr. Trabulsi said. “We found that we can accurately identify foci of prostate cancer within the gland prior to surgery. In fact, we were able to detect lymph node involvement in one patient not seen preoperatively.”
The next study planned is a trial of men with elevated PSA and previously negative biopsies to determine whether PET targeted to VPAC1 can identify areas of prostate cancer within the gland.
“Down the road, we envision studies in men with rising PSA after surgery or radiotherapy to delineate sites of disease, and also studies in metastatic disease to determine if we can assess burden of disease,” Dr. Trabulsi said. “Nirvana would be if we could conjugate VPAC1 to other radiotoxic isotopes for therapeutic purposes.”
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