AJR 2005; 184:676-680
© American Roentgen Ray Society
ProstaScint (Capromab Pendetide) Imaging Using Hybrid Gamma Camera–CT Technology
Terence Z. Wong1,
Timothy G. Turkington1,
Thomas J. Polascik2 and
R. Edward Coleman1
1 Department of Radiology, Division of Nuclear Medicine, Duke University Medical
Center, Box 3949, Durham, NC 27710.
2 Department of Sugery, Division of Urology, Duke University Medical Center,
Durham, NC 27710.
Received April 1, 2004;
accepted after revision June 17, 2004.
Address correspondence to T. Z. Wong
(wong0015{at}mc.duke.edu).
Introduction
Prostate cancer accounts for 33% of all new cancer cases in men, with
230,110 new cases expected to be diagnosed in the United States in 2004.
According to projections for 2004, prostate cancer will account for 10% of all
cancer-related deaths in men and an estimated 29,900 men will die from this
disease [1]. Treatment options
have traditionally included surgery, radiation therapy, and hormonally based
interventions. The optimal therapeutic option depends on the local and
regional extent of disease, which cannot be accurately assessed with current
imaging techniques. In particular, CT and MRI have not proven adequate for
defining regional lymph node involvement. ProstaScint (capromab pendetide,
Cytogen) imaging can improve the prediction of lymph node involvement in
patients at high risk for extraprostatic disease
[2] and therefore can help in
the selection of patients who are candidates for definitive local therapy.
ProstaScint is a murine monoclonal antibody (7E11-C53) that reacts with
prostate membrane specific antigen (PMSA, a membrane glycoprotein different
from PSA), which is highly expressed in prostate cancer. Immunoscintigraphy is
accomplished by labeling the antibody with indium-111. Two major applications
for ProstaScint imaging have been advocated: evaluation of patients with newly
diagnosed prostate cancer, particularly patients with an intermediate to high
Gleason grade who are at risk for advanced disease, and evaluation of patients
who have had definitive local therapy (prostatectomy or radiation therapy) who
present with a rising PSA level. In both situations, ProstaScint imaging may
help one determine whether further local therapy or systemic therapy (i.e.,
hormonal therapy) is indicated. Patients with distant disease would not be
expected to benefit from local radiation therapy or salvage surgical
procedures. However, the interpretation of ProstaScint images is challenging
because of the following factors: the relatively low spatial resolution and
low detection efficiency of medium-energy collimators used for
111In photopeaks; nonspecific antibody localization in the normal
blood pool, bowel, bone marrow, and prostate gland; and lack of anatomic
information to localize radiotracer accumulation. The purpose of our study was
to describe a practical and efficient imaging technique that has been
developed using hybrid gamma camera–CT technology in an effort to
address these problems and to potentially improve the diagnostic accuracy of
this examination.
Materials and Methods
Radiopharmaceutical
Radiolabeling of ProstaScint is performed by adding 220–260 MBq
(6–7 mCi) of buffered 111In chloride to 0.5 mg of capromab
pendetide, as directed by the manufacturer. The patients receive 180–220
MBq (5–6 mCi) of ProstaScint by slow IV injection. No specific bowel
preparation is used, and the patients return 4 days (96 hr) later for
imaging.
Hybrid Gamma Camera–CT Scanner
Imaging is performed on a dual-head scanner (Discovery VH, GE Healthcare)
with an integrated CT scanner built onto the same rotating gantry as the
camera heads [3]
(Fig. 1). The scanner is
equipped with 1-inch (2.54 cm)-thick Starbrite crystals
(Bicron–Saint-Gobain) for more efficient counting of high-energy
photons. Using phantom experiments, we compared count rates using the 1-inch
crystal compared with a standard 3/8-inch (0.95 cm)-thick crystal and found a
59% improvement in the count rate at 245 keV and a 17% improvement at 174 keV.
The Starbrite crystal also features a grid of slots cut into the
photomultiplier side of the crystal to control light spread and small
photomultiplier tubes. These modifications allow the camera to maintain high
spatial resolution for both low- and high-energy radiopharmaceuticals. The
intrinsic spatial resolution is 4.1 mm full-width at half-maximum at 140 keV,
which is comparable to that with conventional 3/8-inch crystals
[4]. The camera has an axial
field of view of 40 cm, and a transaxial field of view of 54 cm.
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Fig. 1. —Photograph shows hybrid SPECT–CT scanner (Discovery VH,
GE Healthcare) equipped with 1-inch (2.54 cm) crystals. CT source
(arrow) and CT detectors are oriented perpendicular to the two gamma
camera heads and rotate on the same gantry.
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All imaging is performed 4 days after the ProstaScint injection. The
patient is asked to void before imaging, and no Foley catheter is used. At the
beginning of the imaging session, the patient receives an IV injection of
CIS-PYRO (99mtechnetium pyrophosphate kit, CIS-US). This provides
2.8–4.9 mg of stannous chloride for in vivo RBC labeling used during the
planar whole-body imaging (discussed in a later section). Because CT is
available for anatomic localization in the pelvis, blood pool imaging is not
required for the SPECT portion of the study, and 99mTc sodium
pertechnetate is not injected until after the SPECT study. SPECT is performed
using symmetric 20% energy windows around the 174-keV and 245-keV
111In photopeaks. A single SPECT examination is performed to image
the pelvis, with the axial field of view set to extend from the scrotum up. A
step-and-shoot technique is used with 45-sec acquisitions at 3°
increments. A 128 x 128 matrix size is used with a zoom factor of 1.4.
Automatic body contouring is used to minimize the collimator-to-body distance.
Total time required for the SPECT examination is approximately 45 min. The
corresponding CT scan of the pelvis is obtained immediately after the SPECT
image acquisition and takes 11 min. CT is performed at 140 kVp with a tube
current of 2 mA with the patient quietly breathing.
After the SPECT and CT examinations, the patient is injected IV with 185
MBq (5 mCi) of 99mTc sodium pertechnetate. Combined with the
previously injected stannous chloride, the 99mTc pertechnetate
provides in vivo RBC labeling for blood pool imaging. The patient is asked to
void again, and anterior and posterior planar images are obtained from the
head to the level of the upper femur using dual-radionuclide acquisition. A
symmetric 20% energy windows is used for the 140-keV 99mTc
pertechnetate photopeak. For the 111In (antibody) images, an
asymmetric energy window setting is used for the 174-keV peak (+10%,
–7.5%), and a symmetric 20% energy window is used for the 247-keV energy
peak. If spot images are obtained, acquisition time is 10 min, and the image
matrix is 256 x 256 pixels with a zoom factor of 1.4. Alternatively,
whole-body images can be acquired contiguously using a table speed of 5
cm/min. Review of the patient imaging and associated clinical data was
approved by the institutional review board of our medical center.
Image Processing
At our institution, image processing and interpretation are performed using
the Xeleris workstation (GE Healthcare). SPECT images are reconstructed using
two iterations of ordered subsets expectation maximization with CT-based
attenuation correction and a final Butterworth filter (10th order, cutoff at
0.26 Nyquist frequency). The interactive display software allows
reconstruction and review of the images in axial, coronal, and sagittal planes
and display of the fused CT and SPECT images.
Results
From May through September 2003, 35 patients were scanned using the
described imaging protocol on the hybrid SPECT–CT scanner. Of these, two
patients (6%) were imaged for staging before therapy and 29 patients (83%)
were imaged after therapy. Four patients (11%) were referred from outside
institutions without clinical data. One patient was scheduled for
prostatectomy, but the procedure was aborted when metastatic pelvic lymph
nodes were identified at surgery.
Of the two patients imaged for initial staging, one patient with a PSA
level of 7.5 ng/mL had diffuse homogeneous radiotracer activity within the
gland and no evidence of distant disease on ProstaScint scanning. At surgery,
this patient was found to have bilateral disease in the prostate gland and
pelvic nodes that were negative for cancer. The second patient (Fig.
2A,
2B,
2C) had heterogeneous
ProstaScint activity in the prostate gland, with focal increased activity in
the right lobe. This finding correlated with the results of a biopsy performed
1 month before the scanning that revealed cancer in both lobes, with Gleason
scores ranging from 5 to 6. The patient's PSA level obtained 4 months before
the scan had been 18.6 ng/mL.
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Fig. 2A. —63-year-old man with newly diagnosed prostate cancer.
Coregistered axial CT (A), SPECT (B), and "fused"
image (C) show focally increased ProstaScint (capromab pendetide,
Cytogen) localization in right lobe, compatible with active prostate
carcinoma. Previous biopsy had revealed disease in both lobes, with Gleason
scores ranging from 5 to 6.
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Fig. 2B. —63-year-old man with newly diagnosed prostate cancer.
Coregistered axial CT (A), SPECT (B), and "fused"
image (C) show focally increased ProstaScint (capromab pendetide,
Cytogen) localization in right lobe, compatible with active prostate
carcinoma. Previous biopsy had revealed disease in both lobes, with Gleason
scores ranging from 5 to 6.
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Fig. 2C. —63-year-old man with newly diagnosed prostate cancer.
Coregistered axial CT (A), SPECT (B), and "fused"
image (C) show focally increased ProstaScint (capromab pendetide,
Cytogen) localization in right lobe, compatible with active prostate
carcinoma. Previous biopsy had revealed disease in both lobes, with Gleason
scores ranging from 5 to 6.
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Of the 29 patients evaluated with ProstaScint imaging after failed local
therapy, 22 (76%) had prior prostatectomy, two (7%) had prior external beam
radiation therapy, and one had both radiation therapy and surgery. In
addition, one patient had hormonal therapy alone, one patient had cryotherapy,
one patient had palladium-seed brachytherapy, and one patient had undergone an
aborted prostatectomy. Correlative PSA values (obtained 
2 months of the
scan) were available for 18 of the patients; the average PSA value was 2.6
ng/mL, with a median value of 0.75 ng/mL and a range of 0.2–20.6 ng/mL.
Twelve patients (41%) had no evidence of local recurrence, 11 patients (38%)
had homogeneous radiotracer accumulation in the prostatic bed that was
suggestive of recurrence, and six patients (21%) had heterogeneous or focal
ProstaScint accumulation in the prostate bed that very strongly suggested
localized recurrent disease. Focal accumulation suggestive of extraprostatic
metastasis was identified in three patients (10%); the sites of abnormal
distant accumulation included a rib in one patient, the skull in a second, and
the retroperitoneum in a third patient. Follow-up examinations of these
patients are still pending.
CT is often helpful in patients after therapy to define posttherapy changes
and to identify residual tissue in the prostatic bed. For example, the images
in Figure 3A,
3B,
3C were obtained after the
patient had undergone failed brachytherapy. Moderately increased activity is
seen throughout the gland, with the implanted seeds clearly visualized. In
this patient, recurrent cancer involving both lobes was confirmed at
biopsy.
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Fig. 3A. —83-year-old man with prostate cancer previously treated with
brachytherapy who presented with increasing PSA level. Corresponding CT
(A), SPECT (B), and "fused" (C) images reveal
implanted palladium seeds and diffuse moderately increased radiotracer
accumulation in prostate gland. Recurrent local disease was confirmed at
biopsy.
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Fig. 3B. —83-year-old man with prostate cancer previously treated with
brachytherapy who presented with increasing PSA level. Corresponding CT
(A), SPECT (B), and "fused" (C) images reveal
implanted palladium seeds and diffuse moderately increased radiotracer
accumulation in prostate gland. Recurrent local disease was confirmed at
biopsy.
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Fig. 3C. —83-year-old man with prostate cancer previously treated with
brachytherapy who presented with increasing PSA level. Corresponding CT
(A), SPECT (B), and "fused" (C) images reveal
implanted palladium seeds and diffuse moderately increased radiotracer
accumulation in prostate gland. Recurrent local disease was confirmed at
biopsy.
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An example of dual-radionuclide planar images is illustrated in
Figure 4. The anterior and
posterior 111In ProstaScint images are displayed beside the
corresponding 99mTc blood pool images. Vascular structures are
observed on both the blood pool and antibody images, and the blood pool images
can aid in distinguishing adenopathy from tortuous vessels on the ProstaScint
scan, particularly in the supraclavicular and inguinal regions. In this
patient, a small focus of ProstaScint accumulation was identified in the
posterior left chest, raising the possibility of a rib metastasis.
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Fig. 4. —70-year-old man with prostate cancer who underwent radical
prostatectomy 6 months earlier and who was being evaluated because of
increasing PSA level. Planar anterior and posterior whole-body ProstaScint
(capromab pendetide, Cytogen)–111indium images (labeled
111In) are shown with corresponding blood pool
(99mtechnetium sodium pertechnetate) images (labeled Tc-99m). Note
mild focal ProstaScint accumulation in supraclavicular and inguinal regions
that corresponds to vascular activity seen on blood pool images. In this
patient, small focus in posterior left chest (arrow, mid torso row,
111In image) also raises question of rib metastasis.
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Discussion
The potential value of ProstaScint imaging in the initial evaluation and
posttreatment follow-up of patients with prostate cancer has been reported in
several studies
[5–9].
In most of these studies, blood pool images were obtained by imaging the
patient immediately after injection of ProstaScint. The planar and SPECT
imaging were then repeated after 4–5 days for the actual antibody
distribution. Blood pool images are used adjunctively with ProstaScint images
to help establish a "road-map" of major vascular structures for
anatomic correlation. Although the use of SPECT–CT eliminates the need
for blood pool imaging in the pelvis, tortuous blood vessels can result in
visualization on planar images of focal ProstaScint accumulation, which can
simulate adenopathy. Corresponding focal activity on the blood pool images
helps to confirm that this finding is attributable to vascular activity rather
than to metastatic adenopathy. For this reason, we continue to include blood
pool imaging as part of our planar imaging protocol.
The use of autologous 99mTc–radiolabeled RBCs for blood
pool imaging, combined with dual-radionuclide imaging, has been advocated by
several groups [10,
11]. The dual-radionuclide
technique cuts imaging time in half because only a single imaging session is
required; in addition, the blood pool and ProstaScint images are acquired
simultaneously and are therefore perfectly aligned. We have adopted the
dual-radionuclide technique, but we further simplify the blood pool imaging
with the use of an in vivo RBC-labeling technique. Because pelvic
SPECT–CT is performed without the use of 99mTc–labeled
RBCs, the antibody images can be acquired using the full 20% 111In
energy window settings. Acquisition efficiency is further improved through the
use of 1-inch-thick crystals on the gamma camera. The in vivo RBC-labeling
technique and dual-radionuclide acquisition are required only for whole-body
planar imaging.
The primary benefit of the coregistered SPECT–CT images is that the
prostate gland and neighboring organs are easily located on the CT scans for
correlation with the SPECT images. ProstaScint activity in the gland is
readily distinguished from adjacent antibody accumulation that frequently
occurs in the rectum and pubic symphysis. Postoperative changes and other
important anatomic features are also provided by the coregistered CT scan. The
concept of spatially correlating ProstaScint SPECT images with CT scans is not
new. Hamilton et al. [12]
reported on a semiautomated technique of coregistering ProstaScint images with
CT scans; image registration was accomplished by defining the major blood
vessels on the blood pool images and aligning these with the CT-defined
vessels. Using a hybrid scanner eliminates this extra step. Hasegawa et al.
[13] developed a prototype of
a SPECT–CT system by configuring a single-head SPECT camera adjacent to
a CT scanner. Anatomic information is particularly helpful preoperatively in
patients with bulky glands or postoperatively in patients who may have
distorted anatomy. Anatomic image correlation may allow more precise
localization of disease in the prostate gland. Ellis et al.
[14] performed image fusion
(also based on vascular structures) between ProstaScint SPECT and CT images in
seven patients. Each patient underwent systematic biopsies in 12 separate
sectors in the prostate, and CT correlation allowed local ProstaScint
accumulation to be correlated with biopsy results. Although theirs was a
relatively small study, Ellis et al. found ProstaScint imaging to have a
sensitivity of 79%, specificity of 80%, and overall accuracy of 80%.
The evaluation of extraprostatic disease in the pelvis and lower abdomen
may also be facilitated by the combined SPECT–CT images. Although the
image quality of CT scans of the abdomen are suboptimal due to respiratory
motion and bowel peristalsis, the scans may be adequate for localizing large
lymph nodes and may aid in distinguishing retroperitoneal or pelvic
lymphadenopathy from physiologic bowel activity. However, our sample size was
too small to evaluate this hypothesis, and the potential value of
SPECT–CT for improving the accuracy of ProstaScint imaging compared with
routine imaging techniques requires further study.
In conclusion, earlier studies have shown the utility of ProstaScint
imaging for initial evaluation of prostate cancer and for evaluation of
recurrent disease in patients after surgery or local radiation therapy.
However, ProstaScint imaging and interpretation remain technically
challenging. We have developed an imaging protocol using a SPECT–CT
scanner that combines the advantages of improved crystal technology for better
111In imaging; SPECT acquisition using dedicated 111In
energy windows for improved count rates; anatomic correlation and
attenuation-correction with CT; and simplified blood pool imaging.
Subjectively, image quality is improved and interpretation is simplified, with
more confident anatomic correlation of antibody localization. However, further
study and follow-up are required to determine whether this technique improves
the accuracy of ProstaScint imaging and in particular whether these technical
improvements translate into significantly improved therapeutic decisions for
patients with prostate cancer.
Acknowledgments
We thank William Sampson and Steven Shipes for technical assistance.
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Materials and Methods
