Comparison of Prostate-Specific Membrane Antigen-Based 18F-DCFBC PET/CT to Conventional Imaging Modalities for Detection of Hormone-Naïve and Castration-Resistant Metastatic Prostate Cancer.
Conventional imaging modalities (CIMs) have limited sensitivity and specificity for detection of metastatic prostate cancer. We examined the potential of a first-in-class radiofluorinated small-molecule inhibitor of prostate-specific membrane antigen (PSMA), N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-(18)F-fluorobenzyl-l-cysteine ((18)F-DCFBC), to detect metastatic hormone-naïve (HNPC) and castration-resistant prostate cancer (CRPC).


METHODS
Seventeen patients were prospectively enrolled (9 HNPC and 8 CRPC); 16 had CIM evidence of new or progressive metastatic prostate cancer and 1 had high clinical suspicion of metastatic disease. (18)F-DCFBC PET/CT imaging was obtained with 2 successive PET scans starting at 2 h after injection. Patients were imaged with CIM at approximately the time of PET. A lesion-by-lesion analysis of PET to CIM was performed in the context of either HNPC or CRPC. The patients were followed with available clinical imaging as a reference standard to determine the true nature of identified lesions on PET and CIM.


RESULTS
On the lesion-by-lesion analysis, (18)F-DCFBC PET was able to detect a larger number of lesions (592 positive with 63 equivocal) than CIM (520 positive with 61 equivocal) overall, in both HNPC and CRPC patients. (18)F-DCFBC PET detection of lymph nodes, bone lesions, and visceral lesions was superior to CIM. When intrapatient clustering effects were considered, (18)F-DCFBC PET was estimated to be positive in a large proportion of lesions that would be negative or equivocal on CIM (0.45). On follow-up, the sensitivity of (18)F-DCFBC PET (0.92) was superior to CIM (0.71). (18)F-DCFBC tumor uptake was increased at the later PET time point (~2.5 h after injection), with background uptake showing a decreasing trend on later PET.


CONCLUSIONS
PET imaging with (18)F-DCFBC, a small-molecule PSMA-targeted radiotracer, detected more lesions than CIM and promises to diagnose and stage patients with metastatic prostate cancer more accurately than current imaging methods.
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Steven P
SP
Rowe
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland Department of Medical Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland; and.
Katarzyna J
KJ
Macura
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Anthony
A
Ciarallo
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Esther
E
Mena
Department of Medical Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Amanda
A
Blackford
Department of Medical Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Rosa
R
Nadal
Department of Medical Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Emmanuel S
ES
Antonarakis
Department of Medical Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Mario A
MA
Eisenberger
Department of Medical Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Michael A
MA
Carducci
The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland; and.
Ashley E
AE
Ross
Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Philip W
PW
Kantoff
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Daniel P
DP
Holt
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Robert F
RF
Dannals
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Ronnie C
RC
Mease
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Martin G
MG
Pomper
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland scho@uwhealth.org.
Steve Y
SY
Cho
D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D043425:Glutamate Carboxypeptidase II / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000000981:diagnostic imaging* / Q000378:metabolism; D014057:Tomography, X-Ray Computed / Q000379:methods*
D000954:Antigens, Surface; C530683:N-(N-((S)-1,3-Dicarboxypropyl)carbamoyl)-4-(18F)fluorobenzyl-L-cysteine; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D003545:Cysteine
bone scan; computed tomography; metastatic prostate cancer; positron emission tomography; prostate-specific membrane antigen