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Title: Comparison of PSMA-based 18F-DCFBC PET/CT to Conventional Imaging Modalities for
Detection of Hormone-Naïve and Castration-Resistant Metastatic Prostate Cancer
Authors: Steven P. Rowe1, Katarzyna J. Macura1,2,3, Anthony Ciarallo1, Esther Mena1, Amanda
Blackford2, Rosa Nadal2, Emmanuel S. Antonarakis2, Mario Eisenberger2, Michael Carducci2,
Ashley Ross3, Philip W. Kantoff4, Daniel P. Holt1, Robert F. Dannals1, Ronnie C. Mease1,
Martin G. Pomper1, and Steve Y. Cho1,5
Author Affiliations: 1The Russell H. Morgan Department of Radiology and Radiological
Science, 2Department of Medical Oncology, and 3The James Buchanan Brady Urological
Institute and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
4Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. 5Present address:
Department of Radiology, University of Wisconsin School of Medicine and Public Health,
Madison, WI, USA.
First Author:
Steven P. Rowe, M.D., Ph.D.
Resident
The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins
Hospital
601 N. Caroline St., Room 3150, Baltimore, MD 21287
(p) (410) 955-6500; srowe8@jhmi.edu
Corresponding Author:
Steve Y. Cho, M.D.
1111 Highland Avenue, WIMR1 Rm 7139
Madison, WI 53705
Office: (608) 263-5048
Fax: (608) 265-7390
Email: scho@uwhealth.org
Running Title: 18F-DCFBC PET/CT of Metastatic Prostate Cancer
Journal of Nuclear Medicine, published on October 22, 2015 as doi:10.2967/jnumed.115.163782
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ABSTRACT
Conventional imaging modalities (CIM) 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), 18F-DCFBC (DCFBC), to
detect metastatic hormone-naïve (HNPC) and castration-resistant prostate cancer (CRPC).
Methods: Seventeen patients were prospectively enrolled (nine HNPC and eight CRPC); 16 had
CIM evidence of new or progressive metastatic prostate cancer and one had high clinical
suspicion of metastatic disease. DCFBC PET/CT imaging was obtained with two successive
PET scans starting at two hours post-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, 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. DCFBC PET detection of lymph nodes, bone lesions, and
visceral lesions was superior to CIM. When intrapatient clustering effects were taken into
account, 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 DCFBC PET (0.92) was
superior to CIM (0.71). DCFBC tumor uptake was increased at the later time PET time point (~
2.5 hr post-injection) with background uptake showing a decreasing trend on later PET.
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Conclusions: PET imaging with DCFBC, a small molecule PSMA-targeted radiotracer, detects
more lesions than CIM and promised to diagnose and stage patients with metastatic prostate
cancer more accurately than current imaging methods.
Key Words: Prostate-specific membrane antigen, metastatic prostate cancer, positron emission
tomography, computed tomography, bone scan.
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INTRODUCTION
Prostate cancer is common, representing the most frequent cancer diagnosis and second
most frequent cause of cancer-related death in men in the United States (1). Many men who
undergo curative therapy for primary prostate cancer will suffer recurrent/metastatic disease.
After a patient demonstrates biochemical recurrence, with newly-appearing or increasing
prostate specific antigen (PSA) blood levels, subsequent treatments such as androgen deprivation
or cytotoxic chemotherapy are often deferred until there has been unequivocal new or
progressive metastatic disease on imaging. That emphasizes the need for imaging of metastatic
prostate cancer to be highly sensitive and specific in order to ensure that patients are treated
appropriately in a timely manner.
Patients suffering biochemical recurrence may be imaged with the conventional imaging
modalities (CIM) of 99mTc-methylene diphosphonate (MDP) bone scan (BS) and contrast-
enhanced CT (CECT) of the chest, abdomen, and pelvis.. There are important limitations to the
sensitivity and specificity of CIM including small (less than 1 cm short axis) lymph nodes that
are not definitively characterized as on CECT; primarily lytic bone lesions that may have little
uptake on BS and be occult on CECT until significant trabecular or cortical destruction has
occurred; and areas of degenerative bone change that are sclerotic on CECT and have high
uptake on BS and that can be mistaken for, or obscure, osteoblastic osseous metastases.
Partly as a result of those limitations, there has been interest in the development of
functional imaging tools for the detection of metastatic prostate cancer. 18F-fluorodeoxyglucose
(FDG) PET/CT, despite widespread use in a variety of cancers, has generally proven to be
problematic in this setting. An array of additional PET radiotracers has been investigated in
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metastatic prostate cancer including those targeting fatty acid metabolism (11C-choline, 18F-
fluorocholine, and 11C-acetate) (2-9) and amino acid transport (anti-1-amino-3-18F-
fluorocyclobutane-1-carboxylic acid, 18F-FACBC) (10-12). Additional radiotracers targeting the
prostate-specific membrane antigen (PSMA) include small-molecule (13-18) and antibody (19-
21) agents . Gastrin releasing peptide (GRP) (22), and glutamine (23, 24) targeted radiotracers
are also being developed.
PSMA is an attractive target for imaging prostate cancer as it is expressed in the vast
majority of prostate cancers and histological studies have associated high PSMA expression with
metastatic spread (25, 26), castration resistance (27-29), and expression levels may be predictive
of progression (30, 31). Our previous work has shown that a radiofluorinated small-molecule
inhibitor of PSMA, N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-[18F]fluorobenzyl-L-cysteine
(DCFBC, Figure 1), was able to concentrate in PSMA-expressing tumors in pre-clinical studies
(14), to identify sites of metastatic disease clinically (13), and to localize at sites of high-grade
primary prostate cancer (32). For this study, we evaluated the ability of DCFBC PET/CT to
identify sites of bone, lymph node, and visceral soft tissue metastatic disease in comparison to
CIM. The study cohort consisted of both hormone-naïve and castration-resistant metastatic
prostate cancer patients.
MATERIALS AND METHODS
Patient Population and Selection
Our hospital’s Institutional Review Board (IRB) approved this study under the auspices
of a Food and Drug Administration exploratory investigation new drug application (eIND
108943). This clinical trial was registered in ClinicalTrials.gov (Identifier: NCT01815515).
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Written, informed consent was obtained from all participating patients. Inclusion criteria for this
study included histologic confirmation of prostate cancer, radiologic evidence of new or
progressive metastatic disease on anatomic or functional imaging and rising prostate specific
antigen (PSA) serum levels on two observations at least one week apart. Exclusion criteria
included the patient being treated with an investigational drug, biologic, or device within 14 days
of DCFBC administration; iniation of new prostate cancer therapy within 14 days of DCFBC
administration; initiation of new therapy for progressive metastatic disease since radiographic
documentation of progression; serum creatinine or total bilirubin greater than 3 times the upper
limit of normal; or liver transaminases greater than 5 times the upper limit of normal. These
baseline laboratory values were obtained to ensure patients were appropriately healthy enough to
reasonably participate in the study. Patients had CECT of the chest, abdomen, and pelvis (single,
venous phase) and planar bone scan within 28 days of DCFBC PET.
Seventeen patients were prospectively enrolled and imaged with DCFBC PET/CT
between May 2013 and May 2014. Patients were followed up to one year with subsequent
imaging examinations obtained at the discretion of the treating medical oncologists.
Radiochemistry
2-[3-(1-Carboxy-2-mercapto-ethyl)-ureido]-pentanedioic acid was synthesized as
previously detailed (33). Non-radioactive DCFBC was prepared according to a modification of a
published protocol with conformation to current good manufacturing practice (14). DCFBC
(radiolabeled) was prepared according to published protocols (13, 34). Specific activity range of
administered DCFBC was 18,837 ± 7,095 mCi/µmol.
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PET/CT Protocol
Patients were asked to remain nil per os (except for water and some medications) for at
least 6 hours prior to the administration of DCFBC. As other investigators have noted the ability
of folate to act as a substrate for PSMA (35-37), we asked that patients not take multivitamins or
folate supplements on the day of DCFBC PET/CT imaging. Blood was drawn and sent for
serum folate, red blood cell folate, and testosterone levels (Table 1).
DCFBC PET/CT images were acquired on a Discovery DRX PET/CT scanner (GE
Healthcare, Waukesha, WI) operating in 3D emission mode with CT-derived attenuation
correction. A bolus injection of 10 ± 1 mCi (370 ± 37 MBq) of DCFBC was administered
intravenously. Two hours post-injection, a whole body (WB, from the top of the skull through
the mid-thighs) CT was obtained [120 kVp, 80 mA maximum (auto-adjusting)] followed by an
initial WB PET acquisition beginning at the mid-thighs with 4 minutes and 15 seconds per bed
position (early time point). Given our earlier experience with DCFBC from the first-in-man
study, we suspected that imaging at a later time point after radiotracer injection might yield
improved tumor uptake and decreased background. Accordingly, immediately following the
initial PET acquisition, a second WB acquisition was obtained, again starting from the mid-
thighs and occurring approximately 2.5 hours post-injection (late time point). PET images were
reconstructed using a clinical ordered subset expectation maximization (OSEM) algorithm.
Image Analysis
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DCFBC PET/CT and BS images were centrally reviewed by 3 expert nuclear medicine
readers (AC, EM, and SYC) who reached a group consensus on the lesions for each scan.
Analyses of the PET/CT and BS images on any one patient were performed at least one week
apart to minimize any bias that might occur in the interpretation of either the PET/CT or BS
based on results from the other study; although the number of patients was relatively small, a
large number of lesions were identified (see results section), decreasing the likelihood that
individual lesions would be recalled and mentally correlated by the central reviewers. CECT
images were centrally reviewed by 2 expert readers (SPR and KJM) who were blinded to the
results of the PET and BS studies and who also reached a group consensus read on each scan.
Visual analysis of DCFBC uptake on the PET/CT scans was performed on a 3-point scale
(1 = negative/below adjacent background, 2 = equivocal/approximately at adjacent background,
and 3 = positive/above adjacent background) on both the early and late time points on a General
Electric Advantage Workstation (GE Healthcare, Waukesha, WI). Maximum standardized
uptake values (SUVmax) corrected for lean body mass were obtained from both time points. For
lesions identified on other modalities that lacked discrete DCFBC uptake, regions of interest
(ROIs) were drawn at corresponding sites on the PET images to derive SUVmax levels for these
lesions. One patient had diffusely infiltrating, biopsy-proven liver metastases that was
interpreted as such by central review of the CECT and was negative (and hence not identified) on
DCFBC PET; this patient’s liver was considered a single lesion for purposes of analysis and
SUVmax was determined from the most confluent focus of disease in the liver. To measure
background, average SUVs (SUVavg) were obtained from ascending aorta blood pool activity,
liver parenchyma in the non-disease-involved right lobe of the liver, within a vertebral body not
involved with disease, and within the right gluteal muscles.
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The BS and CECT images were analyzed on our institution’s standard clinical viewing
software, UltraVisual (Emageon, Birmingham, Alabama, USA). For both modalities, lesions
were again classified on a 3-point scale. For lymph nodes on the CECT scans, a short axis
measurement less than 1 cm was considered negative and a short axis measurement greater than
1 cm was considered positive.
During follow-up of these patients, any available imaging was reviewed by the
appropriate central reviewers. Those lesions that demonstrated subjectively determined
progression or response to therapy on the follow-up studies were considered to be true positive
lesions for purposes of calculating sensitivity. Lesions that remained unchanged were
considered equivocal, and sensitivity was calculated with these equivocal lesions grouped with
either the positive or negative lesions in separate analyses. One patient entered hospice and
subsequently died of his metastatic disease after being imaged with DCFBC PET but before any
imaging follow-up could be completed; the nature of his lesions was established in consultation
between the central imaging reviewers and medical oncologists.
Statistical Analysis
Each lesion was classified as positive, negative, or equivocal by DCFBC PET/CT,
CECT, BS, and combined CIM. The proportion of agreement between modalities was estimated
using intercept-only logistic regression models with a generalized estimating equation (GEE)
approach to account for intra-patient correlation of multiple lesions. In addition to an overall
modality-based analysis, the proportion of agreement was also estimated for lesions based on
location (i.e. lymph node, bone, or visceral soft tissue) as well as patient castrate status (hormone
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naïve versus resistant). Sensitivity was calculated based on follow-up imaging findings using the
GEE intercept-only approach described above. Differences in continuously measured
parameters including SUVmax were estimated with linear regression models using GEE.
Analyses were completed with R version 3.1.2 (38).
RESULTS
Study Population Baseline Imaging
Sixteen out of 17 patients met all inclusion criteria; one patient lacked definite evidence
of new or progressive metastatic disease on imaging, but there was a strong clinical suspicion
that he would have detectable disease with DCFBC PET and the IRB granted an exemption.
Selected clinical and demographic data for the 17 imaged patients are included in Table 1. Of
the 17 patients imaged with DCFBC PET/CT, complete contemporaneous CIM (both CECT of
the chest, abdomen, and pelvis as well as planar WB BS) was available for all but 3 patients.
One patient had a history of severe allergy to iodinated contrast and was imaged with a non-
contrast CT. A second patient had a follow-up CECT at an outside institution but we were not
able to obtain this scan for central review. The third patient had an outside BS, but the images
provided could not be obtained in DICOM format for adequate interpretation.
Imaging Findings
In aggregate, between DCFBC PET and CIM, 714 metastatic lesions were detected on at
least one modality (per patient: median 17 lesions, range 4 to 237). Positive DCFBC PET uptake
was observed visually in 592 lesions with 63 additional lesions deemed equivocal. Overall, for
diagnostic CT, 402 lesions were determined to be positive with an additional 41 determined to be
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equivocal. For BS, 303 lesions were positive and 29 were equivocal. In sum total, 520 lesions
were positive with CIM with a further 61 equivocal lesions.
As shown in Figure 2A, the median and range of SUVmax for DCFBC-positive metastatic
lesions demonstrated higher uptake at the later time point (p < 0.001). The measured
background PET SUVavg trended lower on the later PET time point, though again it was not
statistically significant (Figure 2B). When comparing DCFBC PET-positive metastatic lesions
in patients with HNPC and CRPC, we did not observe a statistically significant difference in PET
SUVmax in the lesions from the two patient populations (p = 0.81 for the early time point and p =
0.57 for the late time point). There was no difference in visual detection of metastatic lesions on
early and later time point PET acquisitions, thus lesion positive/negative/equivocal status
between the two acquisitions was unchanged for all detected lesions.
Statistical Analysis
The general estimating equation estimates for lesion detection by modality are detailed in
Table 2 (the actual number of discrete lesions seen on each modality are included in
Supplemental Table 1). DCFBC PET was able to identify more definitive lesions than CIM.
The estimated proportion of all detected metastatic lesions that would be positive with DCFBC
PET but negative or equivocal with CIM is 0.44 (95% confidence interval (CI) 0.28 – 0.61).
The estimated proportion of lesions that would be positive on CIM but negative or equivocal on
DCFBC PET were 0.08 (95% CI 0.04 – 0.16). The estimated proportions for different types of
metastatic sites are detailed in Table 2.
Despite the concern that high folate levels (defined in our hospital laboratory as >24
ng/mL serum folate) could potentially interfere with DCFBC uptake in cells expressing PSMA,
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the range of number of lesions detected in patients with high folate was similar to the range in
patients with normal folate levels (range 16 – 172 in patients with high folate versus 4 – 237 in
patients with normal folate) with a higher median number of lesions in patients with high folate
(47 in patients with high folate versus 13.5 in patients with normal folate).
Of the original 17 patients recruited, 12 had adequate imaging follow-up to assess for
progression, response, or stability of the lesions originally identified. This follow-up was
generally with conventional imaging only, although a single patient did have a follow-up
research PET scan with a PSMA-targeted radiotracer. Central review of the follow-up imaging
was performed with individual lesions subjectively determined as progressing/responding to
therapy (true lesions) or remaining unchanged (equivocal). Table 3 details the available imaging
and time to follow-up for each patient as well as the intercurrent therapy each received.
Maximum time to follow-up was one year (median time to follow-up was 4 months with range
from 1 month to 1 year). The estimates for sensitivity of DCFBC PET for true metastatic
lesions, with equivocal lesions considered negative for metastasis, was 0.92 (95% CI 0.80 –
0.97) as compared to a sensitivity 0.64 (95% CI 0.41 – 0.82) for CECT, 0.40 (95% CI 0.20 –
0.65) for BS, and 0.71 (95% CI 0.49 – 0.86) for combined CIM (Table 4).
Pertinent examples of imaging findings with DCFBC are shown in Figures 3 – 6 and
Supplemental Figure 1, as detailed in the accompanying figure legends.
DISCUSSION
As noted in the introduction, significant progress has been made in the development of
PET radiotracers for molecular imaging of metastatic prostate cancer, many of which have
demonstrated promise for improving detection relative to CIM. We have presented prospective,
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systematic evidence of the superior sensitivityof the small-molecule PSMA inhibitor DCFBC for
detecting lesions in metastatic prostate cancer patients.
Of particular importance, patients with either HNPC or CRPC were reliably imaged with
DCFBC PET with no statistically significant difference in the observed SUVmax ranges for
metastatic lesions. Given previously published data that had suggested increased PSMA
expression with low androgen signaling, it was of concern that lesions in CRPC patients might
have shown low uptake of a PSMA-targeted radiotracer. Recent clinical data from 68Ga-labeled
PSMA PET radiotracers has also demonstrated that metastatic lesions in CRPC express enough
PSMA to be reliably detected (15, 16).
It is noteworthy that DCFBC PET was capable of showing definitive focal radiotracer
uptake at sites of involvement that are often problematic in the interpretation of conventional
imaging. Sclerotic lesions in the spine on CECT with corresponding MDP uptake on BS may be
interpreted as indeterminate for metastatic involvement versus degenerative change (Figure 3).
Predominantly lytic or mixed bone lesions that can be subtle or are not visualized on CIM can
also be well visualized on DCFBC PET (Figure 4). Furthermore, lymph node metastases that are
too small to definitively identify with CIM can show focal DCFBC uptake (Figure 5).
Analysis of uptake at the early versus late time points suggests that the late time point
produced both improved tumor uptake and decreased background distribution of DCFBC. It is
possible that even later imaging may further improve image quality, although the relatively high
degree of activity within blood pool for DCFBC is likely to persist to at least some degree. The
late time point in this study (approximately 2.5 – 3 hours post injection) is likely to represent a
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suitable compromise between optimizing image quality while preserving reasonable clinical
work-flow.
Potential limitations of DCFBC PET/CT became apparent over the course of this study.
A small number of densely sclerotic bone lesions were much more apparent on CIM (Figure 6).
Although the dense sclerosis and high MDP uptake are indicative of significant bony reaction to
the presence of tumor cells, it may be that these lesions have relatively few metastatic prostate
cancer cells and therefore a diminished ability to sequester PSMA-targeted radiotracers. A
second potential pitfall we observed with DCFBC was in the context of liver metastases, which
were not well seen (Supplemental Figure 1).The reason for this was not immediately apparent,
although we suspect that while metastases are PSMA-avid, signal from such lesions is
overwhelmed by background.
At the initiation of the study, a small minority of patients could not or did not receive
complete baseline CIM, preventing the most complete possible analysis. An additional
significant limitation of this study was the lack of histopathologic truth standard; although we
have attempted to mitigate this by using the surrogate of response to therapy/disease progression
on follow-up imaging to assess for true lesions, this approach remains limited in that lesions
identified on DCFBC PET imaging were necessarily compared to follow-up conventional
imaging. It can also be noted that BS imaging in this study was only planar and tomographic
bone scintigraphy and/or Na18F PET would likely have detected more bone lesions, potentially
narrowing the sensitivity difference between DCFBC PET and CIM.
We recently conducted an initial clinical study with a second generation 18F-labeled
PSMA ligand, 2-(3-(1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-
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pentanedioic acid (DCFPyL), a chemically and mechanistically similar compound to DCFBC but
with higher binding affinity for PSMA and lower activity within blood pool (39). We expect
DCFPyL, as well as additional refinements to other PSMA-binding radiotracers, to address some
of the limitations we have observed. There have been promising results as well for Gallium-68
PSMA radiotracers (15, 16), with advantages easier radiochemistry inherent in a generator
produced Gallium-68 without need for a cyclotron and potential integration to theranostic
applications. We favor the use of Fluorine-18 PSMA agents however, due to ease of distribution
utilizing pre-existing networks for 18F-FDG and improved spatial resolution and more accurate
quantitation inherent in the shorter positron range and higher positron yield of Fluorine-18 versus
Gallium-68 (40). Nonetheless, the systematic prospective evaluation of DCFBC presented here
indicates the promise of PET imaging of PSMA in general as a means to improve detection of
metastatic prostate cancer.
CONCLUSION
PSMA-based PET/CT imaging with DCFBC can detect more metastatic prostate cancer
lesions than the current standard of clinical imaging with CECT and BS in patients with either
HNPC or CRPC. PSMA-targeted imaging offers promise in more accurate identification of the
presence and extent of metastatic prostate cancer.
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DISCLOSURES
None.
ACKNOWLEDGMENTS
We acknowledge funding from the Prostate Cancer Foundation – Young Investigator
Award, RSNA Research & Education Foundation – Research Scholar Award, EB006351,
CA184228, CA183031, and CA134675. We thank Akimosa Jeffrey-Kwanisai and Yavette
Morton for providing dedicated clinical coordination for this trial.
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Figure 3. Anterior projection planar BS (A), DCFBC PET MIP (B), axial CT (C), and axial
DCFBC PET/CT fusion (D) images from a patient thought to have degenerative arthritic changes
at a site of MDP uptake on bone scan (black arrowhead in (A)). However, intense focal DCFBC
uptake was also noted at this site that progressed on follow-up corresponding to a rise in PSA
(black and white arrowheads in B to D).
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Figure 4. DCFBC PET MIP (A), axial CECT (B) and axial fused DCFBC PET/CT (D) images
from a patient with a subtle lytic bone lesion on CT that corresponded to intense DCFBC uptake
in the right posterolateral T5 vertebral body and progressed on follow-up as patient’s PSA level
continued to rise (black and white arrowheads in A to D).
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Figure 5. DCFBC PET MIP (A), axial CECT (B) and axial fused DCFBC PET/CT (C) images
demonstrating intense DCFBC uptake in multiple small pelvic lymph nodes that had been
deemed too small to be definitively disease involved on CECT (black and white arrowheads in A
to D). The lymph nodes decreased in size on follow-up imaging and correlated with a fall in
patient’s PSA level to undetectable.
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Figure 6. Posterior projection planar BS (A), DCFBC PET MIP (posterior view, B), axial CT
(C), axial DCFBC PET (D), and axial fused DCFBC PET/CT (E) images from a patient who was
post-prostatectomy with rising PSA and was naïve to systemic ADT and chemotherapy. Imaging
demonstrates intense MDP uptake on BS and corresponding dense sclerosis on CT of the right
scapula without significant DCFBC uptake (black and white arrowheads in A to E). This lesion
progressed in extent to involve more of the scapula on follow-up imaging in correlation with
rising PSA level in this patient.
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26
Table 1.
Patient
Number
Age PSA
(ng/mL)
Serum
folate
(ng/mL;
normal
2.5-20)
Red cell
Folate
(ng/mL;
normal
160-855)
Testosterone
(ng/dL)
Prior Prostate Cancer Therapy
1 72 81.8 >24 478 <20 Prostatectomy, external beam
radiation to the pelvis, androgen
deprivation
2 83 11.6 14.6 429 245 External beam radiation to the pelvis
3 61 38.9 >24 559 <20 External beam radiation to the
pelvis, androgen deprivation
4 70 8.3 12 268 247 Prostatectomy
5 68 67.6 13.6 361 465 None
6 76 31.4 >24 627 <20 Prostatectomy, androgen
deprivation
7 59 99.6 >24 433 <20 Androgen deprivation, docetaxel,
external beam radiation to the spine
8 69 95.8 18.1 486 <20 External beam radiation to the
pelvis, androgen deprivation
9 69 6.7 17.1 359 <20 Androgen deprivation
10 61 48.3 16.6 N/A 331 Prostatectomy, external beam
radiation to the pelvis
11 73 98.8 >24 N/A 280 Prostatectomy
12 62 564.5 11.8 N/A <20 Androgen deprivation, docetaxel,
tasquinimod, external beam
radiation to the right hip, radium-
223
13 55 62.1 10.3 N/A 442 Prostatectomy
14 58 3.5 11.8 584 273 Prostatectomy, external beam
radiation to the pelvis
15 77 316.1 14.2 860 <20 Androgen deprivation, abiraterone
16 75 6.7 10.4 666 746 Prostate brachytherapy
17 75 83.6 22 1049 538 External beam radiation to the pelvis
Table 1. Selected clinical and demographic data on the patients imaged in this study.
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1
Table 2.
All patients HNPC patients CRPC patients
Modality All
lesions
Lymph
node
lesions
Bone
lesions
Visceral
lesions
All
lesions
Lymph
node
lesions
Bone
lesions
Visceral
lesions
All
lesions
Lymph
node
lesions
Bone
lesions
Visceral
lesions
PET CT BS
Pos Neg/Eq _ 0.30
(0.17 -
0.48)
0.39
(0.21 -
0.62)
0.24
(0.11 -
0.46)
0.18
(0.06 -
0.42)
0.40
(0.20 -
0.65)
0.33
(0.08 -
0.73)
0.34
(0.12 -
0.67)
0.23
(0.07 -
0.56)
0.22
(0.10 -
0.42)
0.50
(0.45 -
0.54)
0.16
(0.05 -
0.42)
0.12
(0.02 -
0.49)
Pos _ Neg/Eq
0.44
(0. 28 -
0.61)
N/A 0.22
(0.12 -
0.36)
N/A 0.55
(0.32 -
0.76)
N/A 0.28
(0.12 -
0.52)
N/A 0.31
(0.14 -
0.57)
N/A 0.18
(0.07 -
0.38)
N/A
Pos Neg/Eq*
0.44
(0.28 -
0.61)
0.90
(0.75 -
0.96)
0.22
(0.12 -
0.36)
0.41
(0.17 -
0.69)
0.55
(0.32 -
0.76)
0.84
(0.44 -
0.97)
0.28
(0.12 -
0.52)
0.39
(0.11 -
0.77)
0.31
(0.14 -
0.57)
0.93
(0.83 -
0.97)
0.18
(0.07 -
0.38)
0.42
(0.12 -
0.80)
Neg/Eq Pos _ 0.07
(0.04 -
0.14)
0.07
(0.01 -
0.39)
0.09
(0.05 -
0.17)
0.05
(0.01 -
0.28)
0.06
(0.01 -
0.24)
0.17
(0.02 -
0.63)
0.07
(0.02 -
0.21)
0.00
(0.00 -
0.00)
0.08
(0.04 -
0.16)
0.00
(0.00 -
0.00)
0.10
(0.04 -
0.21)
0.08
(0.01 -
0.46)
Neg/Eq _ Pos 0.03
(0.01 -
0.08)
N/A 0.05
(0.02 -
0.12)
N/A 0.03
(0.01 -
0.19)
N/A 0.06
(0.01 -
0.29)
N/A 0.03
(0.01 -
0.08)
N/A 0.04
(0.02 -
0.11)
N/A
Neg/Eq Pos*
0.08
(0.04 -
0.16)
0.07
(0.01 -
0.39)
0.10
(0.06 -
0.18)
0.05
(0.01 -
0.28)
0.07
(0.01 -
0.27)
0.17
(0.02 -
0.63)
0.08
(0.02 -
0.27)
0.00
(0.00 -
0.00)
0.09
(0.05 -
0.17)
0.00
(0.00 -
0.00)
0.11
(0.06 -
0.21)
0.08
(0.01 -
0.46)
* Combined CIM (CT and BS)
Table 2. Estimated proportion of agreement in metastatic lesions detection between the PET and CIM, accounting for intrapatient
clustering effects by GEE regression model analysis. 95% confidence intervals are included in parentheses.
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1
Table 3.
Patient Number Therapy following
DCFBC PET
Time to imaging
follow-up
Follow-up imaging
modalities available
1 Started sipuleucel-T 6 months Na18F PET/CT
2 Started androgen
deprivation
4 months BS
3 Continued androgen
deprivation
N/A N/A
4 Started androgen
deprivation
2 months CECT, BS
5 Started androgen
deprivation
6 months CECT, BS
6 Started cabazitaxel 4 months CECT, BS
7 Entered hospice N/A N/A
8 Continued androgen
deprivation
N/A N/A
9 External beam
radiation to the
pelvis, continued
androgen deprivation
4 months CECT, BS
10 Started androgen
deprivation
N/A N/A
11 Started androgen
deprivation
6 months CECT, BS
12 Continued radium-
223
3 months CECT, BS
13 Started androgen
deprivation
1 year PSMA PET/CT
14 External beam
radiation to pelvic
lymph node, started
nelfinavir
3 months CECT
15 Continued androgen
deprivation, started
veliparib
3 months CECT, BS
16 No follow-up
information available
N/A N/A
17 Started androgen
deprivation
1 month CECT
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2
Table 3. List of prostate cancer therapies received by the patients in this study in the follow-up
period after DCFBC PET imaging. The time to follow-up and available modalities at follow-up
are also noted. Patient 13 underwent follow-up PET/CT imaging with a different PSMA targeted
radiotracer (18F-DCFPyL) than the one primarily described here.
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3
Table 4.
Modality Sensitivity
[Equivocal Lesions
Considered Negative]
(95% CI)
Sensitivity
[Equivocal Lesions
Considered Positive]
(95% CI)
DCFBC PET 0.92 (0.80 – 0.97) 0.88 (0.70 – 0.96)
CECT 0.64 (0.41 – 0.82) 0.77 (0.58 – 0.89)
BS 0.40 (0.20 – 0.65) 0.43 (0.25 – 0.63)
CIM
(BS and CECT)
0.71 (0.49 – 0.86) 0.82 (0.60 – 0.93)
Table 4. Sensitivity, with equivocal lesions considered either positive or negative for metastases
in two separate analyses, for DCFBC PET and CIM as estimated by GEE regression model
analysis. The 95% confidence intervals are included in parentheses.
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Doi: 10.2967/jnumed.115.163782
Published online: October 22, 2015.
J Nucl Med.
C Mease, Martin G. Pomper and Steve Y Cho
Antonarakis, Mario Eisenberger, Michael Carducci, Ashley Ross, Philip Kantoff, Daniel P Holt, Robert F Dannals, Ronnie
Steven P. Rowe, Katarzyna J Macura, Anthony Ciarallo, Esther Mena, Amanda Blackford, Rosa Nadal, Emmanuel
Cancer
for Detection of Hormone-Sensitive and Castration-Resistant Metastatic Prostate
F-DCFBC PET/CT to Conventional Imaging Modalities
18
Comparison of PSMA-based
http://jnm.snmjournals.org/content/early/2015/10/21/jnumed.115.163782
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