title: ¹⁸F-DCFBC PET/CT for PSMA-Based Detection and Characterization of Primary Prostate Cancer.
abstract: We previously demonstrated the ability to detect metastatic prostate cancer using N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-(18)F-fluorobenzyl-L-cysteine ((18)F-DCFBC), a low-molecular-weight radiotracer that targets the prostate-specific membrane antigen (PSMA). PSMA has been shown to be associated with higher Gleason grade and more aggressive disease. An imaging biomarker able to detect clinically significant high-grade primary prostate cancer reliably would address an unmet clinical need by allowing for risk-adapted patient management.
  
  
  METHODS
  We enrolled 13 patients with primary prostate cancer who were imaged with (18)F-DCFBC PET before scheduled prostatectomy, with 12 of these patients also undergoing pelvic prostate MR imaging. Prostate (18)F-DCFBC PET was correlated with MR imaging and histologic and immunohistochemical analysis on a prostate-segment (12 regions) and dominant-lesion basis. There were no incidental extraprostatic findings on PET suggestive of metastatic disease.
  
  
  RESULTS
  MR imaging was more sensitive than (18)F-DCFBC PET for detection of primary prostate cancer on a per-segment (sensitivities of up to 0.17 and 0.39 for PET and MR imaging, respectively) and per-dominant-lesion analysis (sensitivities of 0.46 and 0.92 for PET and MR imaging, respectively). However, (18)F-DCFBC PET was more specific than MR imaging by per-segment analysis (specificities of 0.96 and 0.89 for PET and MR imaging for corresponding sensitivity, respectively) and specific for detection of high-grade lesions (Gleason 8 and 9) greater than 1.0 mL in size (4/4 of these patients positive by PET). (18)F-DCFBC uptake in tumors was positively correlated with Gleason score (ρ = 0.64; PSMA expression, ρ = 0.47; and prostate-specific antigen, ρ = 0.52). There was significantly lower (18)F-DCFBC uptake in benign prostatic hypertrophy than primary tumors (median maximum standardized uptake value, 2.2 vs. 3.5; P = 0.004).
  
  
  CONCLUSIONS
  Although the sensitivity of (18)F-DCFBC for primary prostate cancer was less than MR imaging, (18)F-DCFBC PET was able to detect the more clinically significant high-grade and larger-volume tumors (Gleason score 8 and 9) with higher specificity than MR imaging. In particular, there was relatively low (18)F-DCFBC PET uptake in benign prostatic hypertrophy lesions, compared with cancer in the prostate, which may allow for more specific detection of primary prostate cancer by (18)F-DCFBC PET. This study demonstrates the utility of PSMA-based PET, which may be used in conjunction with MR imaging to identify clinically significant prostate cancer.
authors.affiliation: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Rowe
authors.affiliation: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Gage
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Sheila F
authors.initials: SF
authors.lastname: Faraj
authors.affiliation: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.|The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland.|Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Katarzyna J
authors.initials: KJ
authors.lastname: Macura
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Toby C
authors.initials: TC
authors.lastname: Cornish
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Nilda
authors.initials: N
authors.lastname: Gonzalez-Roibon
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Gunes
authors.initials: G
authors.lastname: Guner
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Enrico
authors.initials: E
authors.lastname: Munari
authors.affiliation: The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Partin
authors.affiliation: The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Pavlovich
authors.affiliation: The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Misop
authors.initials: M
authors.lastname: Han
authors.affiliation: The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: H Ballentine
authors.initials: HB
authors.lastname: Carter
authors.affiliation: The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Trinity J
authors.initials: TJ
authors.lastname: Bivalacqua
authors.affiliation: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Amanda
authors.initials: A
authors.lastname: Blackford
authors.affiliation: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Holt
authors.affiliation: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Dannals
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland.|The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland.|Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
authors.affiliation: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Lodge
authors.affiliation: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Ronnie C
authors.initials: RC
authors.lastname: Mease
authors.affiliation: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
authors.affiliation: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.|Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Steve Y
authors.initials: SY
authors.lastname: Cho
mesh_terms: D000368:Aged; D000954:Antigens, Surface / Q000737:chemistry; D014408:Biomarkers, Tumor / Q000737:chemistry; D001706:Biopsy; D003545:Cysteine / Q000031:analogs & derivatives*; D019788:Fluorodeoxyglucose F18; D043425:Glutamate Carboxypeptidase II / Q000737:chemistry; D006801:Humans; D006984:Hypertrophy; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D049268:Positron-Emission Tomography; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging*; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed
chemical_list: D000954:Antigens, Surface; D014408:Biomarkers, Tumor; C530683:N-(N-((S)-1,3-Dicarboxypropyl)carbamoyl)-4-(18F)fluorobenzyl-L-cysteine; D019788:Fluorodeoxyglucose F18; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D003545:Cysteine
keywords: MRI; PET/CT; primary prostate cancer; prostate specific membrane antigen (PSMA); prostatectomy