psma-based 18f-dcfpyl pet/ct and pet/mri pilot studies in prostate cancer

Conditions: Prostate Cancer; Prostate Neoplasm

Summary: the overall goal of this research is to validate and develop a non-invasive imaging biomarker of prostate cancer detection, progression, and recurrence. development of such a biomarker may be useful to differentiate indolent from aggressive prostate cancer phenotypes allowing for selection of an appropriate risk adaptive therapy.

the investigators propose to evaluate a novel second-generation low-molecular-weight prostate specific membrane antigen (psma)-based positron emission tomography (pet) agent, 18f-dcfpyl, for detection of primary and metastatic prostate cancer. 18f-dcfpyl pet demonstrates very high tumor-to-background and tumor specific uptake which may allow for a more sensitive and accurate method for detection of early tumor recurrence and metastatic disease as compared to current pet radiotracers and current standard-of-care imaging including 99mtc-methylene diphosphonate bone scintigraphy (bone scan), contrast-enhanced computed tomography (ct) and magnetic resonance imaging (mri). primary objectives: the investigators propose to evaluate this pet agent for four different prostate cancer clinical scenarios. 1. detection of clinically significant high-grade prostate cancer and initial staging 2. detection of sites of recurrence in the setting of biochemical recurrence after definitive prostatectomy 3. detection of advanced androgen-resistant metastatic prostate cancer, and 4. detection of clinically significant prostate cancer in very low to intermediate risk primary prostate cancer secondary objectives: * evaluate the performance of 18f-dcfpyl pet and mri whole body dwi for detection of local-nodal and distant metastatic disease on initial staging compared to conventional imaging modalities (ct and bone scintigraphy). * correlate 18f-dcfpyl pet standardized-uptake values (suv) and mri parameters with psma expression by prostatectomy pathology ihc. * evaluate the specificity of 18f-dcfpyl pet for differentiating primary prostate cancer versus non-malignant prostate lesions (bph, prostatitis). * comparison of whole body low-dose ct and whole body mri derived pet suv-quantitation. * evaluate the performance of dedicated pelvic 18f-dcfpyl pet/mri with dynamic pet acquisition and multi-parametric mri for differentiation of urine versus recurrent malignancy in the prostatectomy bed. * evaluate the contribution of whole body mri dwi obtained from pet/mri to improve the diagnostic performance of 18f-dcfpyl pet/ct and pet/mri for metastatic prostate cancer lesion detection. * assess the quantitative accuracy of pet-derived standardized uptake value (suv)-based parameters in 18f-dcfpyl pet obtained from pet/mri versus pet/ct. * assess the quantitative reproducibility of 18f-dcfpyl pet/ct derived-suv values in normal organ and metastatic tumor lesions. * evaluate the ability of 18f-dcfpyl pet to improve detection of clinically significant primary prostate cancer in men with very low to intermediate risk prostate cancer under active surveillance or watchful waiting. update: as of july 2022 verification, the investigators are no longer enrolling into sub-studies 1 and 2.

Eligibility criteria:
inclusion criteria: * prostate cancer pathologically proven by prostate biopsy (newly diagnosed for sub-study 1 and 4) * prostate biopsy histology grade ≥ gleason 1, 6, 3+4, or 4+3; positive biopsy \>2 cores * any psa permitted * two consecutive rising psa values (sub-study 3 only) * castrate-levels of testosterone - total testosterone \< 50 ng/dl (sub-study 3 only) * patients considered as candidates for and medically fit to undergo prostatectomy * at least 7 days after most recent prostate biopsy * imaging evidence of suspected metastatic disease, including ct, bone scan, mri, ultrasound or other pet modalities (sub-study 3 only) * new diagnosis of prostate cancer undergoing additional biopsy evaluation (sub--study 4 only) * karnofsky performance status of at least 70 (sub-study 4 only) * general health and anatomy suitable to undergo transrectal ultrasound-mri fusion biopsy of the identified lesions and standard 12 core sextent biopsy (sub-study 4 only) exclusion criteria: * prior pelvic external beam radiation therapy or brachytherapy * chemotherapy for prostate cancer * androgen deprivation therapy for prostate cancer * investigational therapy for prostate cancer (sub-study 3 only) * unable to lie flat during or tolerate pet/ct * prior history of any other malignancy within the last 2 years, other than skin basal cell or cutaneous superficial squamous cell carcinoma that has not metastasized and superficial bladder cancer. * no prostatectomy scheduled more than 12 hours post imaging (sub-study 1 only) * serum creatinine \> 2 time the upper limit of normal * total bilirubin \> 3 times the upper limit of normal * liver transaminases \> 5 times the upper limit of normal

Keywords: prostate cancer prostate neoplasm