PET/CT P In The News

Issue No.11 October 2010
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Table of Contents
In the News
...............................p 1 - 3, 5-7
Case Study of the Month
...........................................p 4
Next Issue: December
In The News
PET/CT detects early efficacy of chemo drug in NSCLC patients
By Wayne Forrest staff writer
September 17, 2010
Dutch researchers have found that FDG-PET/CT can
identify early response to preoperative chemotherapy
with erlotinib in most patients with non-small
cell lung cancer (NSCLC), potentially avoiding
unnecessary toxicity from ineffective treatment,
according to a study in the September issue of the
Journal of Nuclear Medicine.
Though the study was relatively small, the researchers
from four hospitals in the Netherlands concluded
that the results are promising and consistent with
the results of preclinical studies. The lead author was
Tjeerd Aukema, MD, from the department of nuclear
medicine at Haga Hospital in the Hague (JNM,
September 2010, Vol. 51:9, pp. 1344-1348).
Erlotinib, an epidermal growth factor receptor (EGFR)
tyrosine kinase inhibitor, has been used over the
past several years to treat non-small cell lung cancer.
Previous research has found that the moleculartargeted agent can prompt early responses to
treatment in certain patients with NSCLC and prolong
survival when administered as a second-line treatment
in advanced cases.
NSCLC survival
The survival rate for NSCLC patients has not
improved greatly over the past few years, the authors
wrote, and the number of patients presenting with
stage IV disease has increased. They noted that
the advance is likely the result of better staging, as
the metastatic disease is identified prior to clinical
symptoms, in part, through FDG-PET’s ability to
determine oncologic staging.
Positron Emission Tomography (PET) is a
non-invasive diagnostic imaging procedure
that can provide unique information for
accurate TNM staging. Many cancers
exhibit increased glucose metabolic rates
which can be identified with PET via the
radio-pharmaceutical 18F-FDG. Since
changes in glucose metabolism often
occur before changes in anatomy (e.g.
tumor growth), PET can often identify
the presence of disease earlier than other
anatomic imaging techniques. Early
disease identification is particularly
critical during the assessment of nodal
involvement or the determination of the
presence of metastatic disease.
additional endoscopic ultrasound-guided fine-needle
aspiration cytology or mediastinoscopy was used.
Erlotinib treatment
The patients received preoperative erlotinib (150 mg)
once daily for three weeks, with FDG-PET/CT scans
performed before and after erlotinib administration
to obtain both baseline FDG-PET/CT and follow-up
results. The median time between the start of erlotinib
therapy and follow-up FDG-PET/CT imaging was six
The baseline FDG-PET/CT scans (Gemini TF, Philips
Healthcare, Andover, MA) were obtained during
routine staging in all patients with FDG doses of 180
to 240 MBq. Low-dose CT images also were acquired
without intravenous contrast. The median time
between these two scans was 21 days.
The researchers measured changes in tumor FDG
uptake during treatment by prospectively assessing
standardized uptake values (SUVs). Patients with
a decrease in SUV of 25% or more after one week
were classified as “metabolic responders.” Their
metabolic response was compared with the pathologic
response, which was obtained through histopathologic
examination of resected specimens.
SUV comparisons
Aukema and colleagues found the median SUVmax
at baseline FDG-PET/CT to be 11.0, while the median
SUVmax after one week of erlotinib therapy was 9.3.
In addition, six (26%) of the 23 cases had a partial
response within one week, 16 patients (70%) had
stable disease, and one patient (4%) had progressive
Therefore, they hypothesized that FDG-PET/CT may
be a “valuable clinical predictor” for early response to
preoperative erlotinib treatment.
The study enrolled eight men and 15 women (mean
age, 63 years) from October 2006 to March 2009. All 23
patients were diagnosed with stage I to stage III nonsmall cell lung cancer and were eligible for surgical
resection. They also were part of an ongoing phase II
trial at the four Dutch hospitals of the researchers.
Staging procedures included contrast-enhanced CT
and PET/CT scans. With mediastinal metabolic uptake
or nodes greater than 1 cm in the shortest diameter,
Coronal FDG-PET images show a patient with carcinoma in the left lung.
Maximum intensity projection (MIP) images before (A) treatment with
erlotinib show a reduction in uptake (ΔSUVmax, -57%) and increase in
necrosis of primary tumor after seven days (B) of treatment with erlotinib.
The results are also noted in transverse PET/CT fusion images before (C) and
after seven days (D) of erlotinib. After erlotinib treatment, the patient was
operated on; the resected specimen contained 80% necrosis. Image courtesy of
the Journal of Nuclear Medicine.
In the News
FDG-PET/CT also revealed a median 40% necrosis in the
resection specimens of treated patients. Among patients
classified as metabolic responders, the median percentage
necrosis was 70%, compared with a median 40% necrosis
among metabolic nonresponders.
The prospective study suggests that during the course of
preoperative erlotinib treatment for NSCLC patients, FDG-
PET/CT “can identify response in most patients,” the authors
concluded. “Even though our study was relatively small,
the results are promising and consistent with the results of
preclinical studies.”
They recommended that additional data from larger groups
of patients are needed to definitively determine “the optimal
timing of response evaluation and the relevance of cutoff
values of response parameters.”
PET-CT Can Detect Asymptomatic Recurrence of Head and Neck
Cancer: Presented at AAO-HNSF
By Cheryl Lathrop
September 30, 2010
BOSTON -- September 30, 2010 -- Positron emission
tomography (PET) and conventional computed
tomography (CT) is an effective tool for detecting
early asymptomatic recurrent disease, according to a
study presented here on September 27 at the American
Academy of Otolaryngology-Head and Neck Surgery
Foundation (AAO-HNSF) Annual Meeting 2010.
Head and neck cancer patients are at greatest risk of
recurrence within the first 5 years of treatment, but early
detection of recurrent disease in patients with a benign
exam, and no symptoms, is a challenge, according to
findings presented during a poster session by Mark
Varvares, MD, Department of Otolaryngology-Head and
Neck Surgery, St. Louis University, St. Louis, Missouri,
and colleagues.
Previous studies have shown the PET-CT imaging
modality to be more accurate than PET alone. And,
it could detect disease that would otherwise not be
identified upon physical exam or by patient-reported
symptoms. The researchers recently reported the
effectiveness of fluorodeoxyglucose (FDG) PET-CT
in detecting an asymptomatic recurrence in a group
of previously treated head and neck cancer patients.
This report is a follow-up study reporting the survival
outcomes in this group once the recurrence was detected.
A retrospective review was performed on a series of head
and neck cancer patients (n = 123) at a single institution
between February 2004 and July 2007 who had undergone
non-staging FDG-PET-CT scans as an integral part of
the patient’s follow up after having received definitive
treatment. Each scan (n = 308) was evaluated by a
board-certified nuclear medicine physician and final
scan readings from each patient’s medical record were
reviewed for this study.
Lesions were defined as primary, regional, or distant
site. Each positive lesion was confirmed clinically
or histologically, and each positive lesion was then
retrospectively defined as symptomatic or asymptomatic
Page 2
based on clinic notes. Lesions were considered to be an
asymptomatic recurrence if the patient had no symptoms
or physical findings at the time of the scan. The patients
who were identified as having an asymptomatic
recurrence were then followed until the time of their last
follow-up visit, or death.
The majority of patients evaluated had squamous cell
carcinoma of the oral cavity, pharynx, and larynx. There
were 96 (78%) male patients and 27 (22%) female patients.
A total of 616 lesions on 308 scans were evaluated. Of
those scans, 25 (8%) detected asymptomatic disease;
33 (5%) represented asymptomatic recurrent disease.
Asymptomatic lesions were detected most frequently at
distant sites with 52% being thoracic, but also included
primary (6%), regional (9%), and other (33%) sites. These
lesions were found in 24 (20%) of the patients evaluated.
At last follow-up of the 24 patients where asymptomatic
recurrence was detected, 9 remain alive, 5 with disease.
The remainder of the group has died of malignant disease.
“Determining an effective surveillance regimen is the goal
for future management of head and neck malignancies;
prospective studies are necessary to determine if PETCT imaging modality will be part of this routine,” Dr.
Varvares noted.
FDG-PET/CT viability scans
detect vulnerable aortic plaque
By Wayne Forrest staff writer
September 27, 2010
Canadian researchers have found that detecting
vulnerable aortic plaque with conventional FDG-PET/
CT myocardial viability studies is feasible, according
to a presentation at the American Society of Nuclear
Cardiology (ASNC) annual meeting in Philadelphia.
The group, from the University of Ottawa Heart Institute
in Ottawa, Ontario, also found that the rate of very
positive FDG uptake among patients with ischemic
heart disease is low, which reflects aggressive secondary risk factor
modification through statins and lip-lowering drugs.
FDG-PET/CT myocardial viability scans are routinely used on
patients with severe coronary artery disease and left ventricular
dysfunction, because FDG accumulates in areas with high levels
of metabolism including vulnerable aortic plaque, according to the
The three images represent clinical myocardial FDGPET/CT viability studies, which show Grade 0 or
negative aortic FDG uptake (A), Grade 1 or mildly
positive aortic FDG uptake (B), and Grade 2 or very
positive aortic 18-FDG uptake (C). Images courtesy of
the University of Ottawa Heart Institute.
Statins also have been shown to significantly reduce the degree of
aortic FDG uptake. “Since the imaging window of FDG-PET/CT
scans includes the aorta, we evaluated the feasibility of vulnerable
plaque detection using the cardiac FDG-PET viability studies,”
noted senior study author Terrence Ruddy, MD, director of nuclear
medicine at the Heart Institute and head of nuclear medicine at
Ottawa Hospital, and colleagues.
Myocardial viability scans
The researchers retrospectively analyzed FDG uptake in 30
consecutive patients, 24 men and six women, who received FDGPET myocardial viability scans and had a history of coronary artery
disease. In addition, 28 of the 30 patients were being treated with
statins or other lipid-lowering agents.
PET/CT, Prostate Cancer After Surgery
By: Jeff Muise
Friday, August 27, 2010
All 30 myocardial viability studies were reconstructed with PET
and CT registration based on extracardiac landmarks to avoid
attenuation correction artifacts. The study also used the lumen of
the descending thoracic aorta to determine the blood pool standard
uptake value (SUV) of FDG.
(HealthDay News) — Positron emission tomography/computerized
tomography (PET/CT) to detect [11C]choline uptake appears to
be useful for re-evaluating prostate cancer disease stage for men
who have increasing prostate-specific antigen (PSA) levels after
radical prostatectomy and no evidence of disease on conventional
imaging, according to a study in the September issue of The Journal
of Urology.
The researchers then evaluated the areas of FDG uptake and activity
relative to blood pool. Grade 0 or negative evaluation was given to
areas with no activity, or if the average SUV to blood pool average
SUV ratio was less than 1.25. Grade 1 or mildly positive activity
indicated a ratio of average SUV to blood pool average SUV of 1.25
to 1.50. Grade 2 or very positive activity indicated that the ratio of
average SUV to blood pool average SUV was greater than 1.50.
Giampiero Giovacchini, M.D., of the University of Milano-Bicocca
in Italy, and colleagues studied 109 patients who had PSA levels
above 0.2 ng/mL after radical prostatectomy, no lymph node disease
at prostatectomy, no evidence of metastatic disease on conventional
imaging, no androgen deprivation therapy, and no radiotherapy.
The subjects underwent [11C]choline PET/CT to re-evaluate their
prostate cancer disease stage.
FDG uptake
The analysis found that six (17%) of the 30 studies had grade 2 or
very positive FDG uptake, while 19 studies (63%) had grade 1 or
mildly positive FDG uptake. The remaining five studies (17%) had
little or no FDG uptake.
The researchers found that the PSA counts in the group at time of
imaging ranged from 0.22 to 16.76 ng/mL (median 0.81 ng/mL).
Based on the PET/CT imaging, local recurrence was diagnosed in
four patients (4 percent) and pelvic lymph node disease in eight
patients (7 percent). Scans were positive in 5 percent of patients with
PSA less than 1 ng/mL, 15 percent with PSA between 1 and 2 ng/mL,
and 28 percent with PSA greater than 2 ng/mL.
Five of the six patients with grade 2 or very positive uptake were
on a lipid-lowering agent. In addition, 19 of 20 patients with grade
1 mildly positive uptake were on a lipid-lowering agent. All five
patients with grade 0 negative uptake were on a lipid-lowering
Based on the results, Ruddy and colleagues concluded that detecting
vulnerable aortic plaque with conventional FDG-PET/CT viability
scans is feasible. “The rate of very positive uptake in this population
of ischemic heart disease patients is low, reflecting aggressive
secondary risk factor modification” and showing the value of statins
and lipid-lowering agents.
“Positron emission tomography/computerized tomography detected
increased [11C]choline uptake, suggesting recurrent disease in 11
percent of patients with prostate cancer, increasing PSA after radical
prostatectomy, and no evidence of disease on conventional imaging.
This modality may be useful to restage disease but it cannot be used
to guide therapy,” the authors write.
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Case Study of the month
F-NaF PET bone imaging vs. planar 99mTc MDP in a patient
with breast cancer
The following case (Figure 1 and Figure 2 ) shows a
patient with a history of breast cancer who presented
with increasing back pain two weeks after a fall. The
99mTc-MDP planar bone scan showed increased uptake
in the body of the L2 vertebrae, which suggested the
possibility of post-traumatic fracture or metastatic
disease. A minimal focal uptake in the left 7th rib was
also similarly equivocal. MRI of the lumbar spine showed
focal marrow hyperintensities, which were suspicious for
bone metastases. An 18F-FDG PET scan was performed,
which showed no abnormal vertebral lesion. In view
of the fact that FDG PET is often normal in presence of
purely sclerotic bone metastases, a 18F-NaF PET scan was
ordered. The 18F-NaF scan revealed abnormal uptake
consistent with metastatic disease in the vertebral body
of the L2 vertebra. Additional foci were noted in vertebral
bodies L3, L5, the superior end plate of L4, and the
right transverse process of L3; all were consistent with
metastatic bone disease that was not visualized in the
FDG PET scan. Numerous lesions that were identified in
the pelvis were appreciated only in retrospect on a prior
CT scan. Focal uptake in the left 7th rib and right glenoid
were consistent with metastatic disease. An additional
focus of activity was seen in the proximal metaphysis of
the right femur that was faintly visualized on the bone
Figure 1. 18F-NaF PET bone imaging vs. planar 99mTc MDP in a patient with breast cancer
Data courtesy David Haseley, MD and Gustavo Mercier, MD, Seattle Nuclear Medicine, Seattle, WA
Tc MDP Bone Scan
Page 4
Continued on page 5
Figure 2. 18F-NaF PET bone imaging vs. planar 99mTc MDP in a patient with breast cancer - continued
Data courtesy David Haseley, MD and Gustavo Mercier, MD, Seattle Nuclear Medicine, Seattle, WA
mTc MDP Bone Scan
Page 5
Study combines FDG-PET/
CT with circulating tumor
cell counts
The retrospective study reviewed the M. D. Anderson
breast medical oncology database and identified patients
who had received systemic treatment for bone metastases
from breast cancer between December 2004 and May
2008, as well as patients with intrathoracic lymph node
or chest wall metastases in addition to bone metastases.
Patients with visceral metastases were excluded.
All 55 patients enrolled in the study underwent FDGPET/CT scans (Discovery ST, STE, or RX, with 8-, 16-, or
64-slice CT, GE Healthcare, Chalfont St. Giles, U.K.) and
CTC evaluation within three weeks before starting a new
By Wayne Forrest staff writer
August 26, 2010
August 26, 2010 -- Although FDG-PET/CT is useful for
monitoring patients with bone metastases from breast
cancer, additional prospective studies are needed to
define the roles of FDG-PET/CT and circulating tumor
cells in measuring the disease, according to a new study
in the August issue of the Journal of Nuclear Medicine.
Circulating tumor cells (CTCs) are cells that can break
from a tumor, travel through the bloodstream, and
eventually become tumors in organs such as the breast,
liver, or colon. The presence of CTCs before treatment
is a predictor of progression-free survival and overall
survival in patients with metastatic breast cancer.
Researchers from M. D. Anderson Cancer Center at the
University of Texas in Houston found that CTC counts at
follow-up agreed with FDG-PET/CT assessment in 78%
of the study’s patients. In addition, FDG-PET/CT findings
and follow-up CTC counts were “significantly associated
with both progression-free survival and overall survival.”
The lead author of the study was Ugo De Giorgi, MD,
from the department of breast medical oncology at M. D.
Anderson (JNM, August 2010, Vol. 51:8, pp. 1213-1218).
CTC numbers
Another study by De Giorgi and colleagues, published
earlier this year in the Annals of Oncology, found that
the presence of extensive bone metastases as detected
by FDG-PET/CT was associated with increased CTC
numbers in metastatic breast cancer (Ann Oncol, January
2010, Vol. 21:1, pp. 33-39).
“Specifically, we showed that CTC numbers were higher
in patients with bone metastases than in those with no
bone lesions and higher in patients with three or more
old metastases than in those with fewer bone lesions,” the
authors wrote.
With that as the foundation, the authors launched a new
study to compare the predictive significance of FDG-PET/
CT and CTC counts in patients with bone metastases
from breast cancer treated with standard systemic
Page 6
Twenty-six patients received systemic therapies for bone
metastases only, and 29 patients received treatment for
bone metastases and intrathoracic lymph node or chest
wall metastases after undergoing both CTC and PET/CT
Thirty-six patients (65%) had received prior treatment for
metastatic breast cancer with hormone therapy (23 cases),
chemotherapy with or without hormone therapy (nine
cases), or HER2-targeted therapies with chemotherapy
or hormone therapy (four cases). Nineteen patients (35%)
had newly diagnosed metastatic breast cancer.
Disease progression
In their analysis, the researchers found CTC count at
follow-up agreed with the FDG-PET/CT assessment
for nonprogressive disease or progressive disease in 43
patients (78%).
Among the remaining patients, four patients (33%)
with fewer than five circulating tumor cells per 7.5 mL
of blood at follow-up were found to have evidence of
progressive disease by FDG-PET/CT, compared with
eight patients (67%) with persistent CTCs (≥ 5 CTCs/7.5
mL of blood) at follow-up who did not have evidence of
progressive disease.
In all 55 patients, the mean for progression-free survival
was 10.5 ± 7.2 months, ranging from two to 34 months.
The mean overall survival was 18.1 ± 6.7 months, with a
range of three to 37 months.
At the time of analysis, seven patients (13%) were
considered progression-free, with an average followup time of 18 months, ranging from 10 to 34 months.
Eighteen patients (33%) had died.
Follow-up CTC counts and FDG-PET/CT assessment for
nonprogressive or progressive disease were found to be
significantly associated with both progression-free and
overall survival. The researchers also concluded that
baseline CTC count was “not a significant predictor for
either progression-free survival or overall survival.”
The group also found that median progression-free survival
was 13 months in patients with both < 5 CTCs/7.5 mL of blood
and FDG-PET/CT nonprogression. The median progression-free
survival was six months in patients with < 5 CTCs/7.5 mL of blood
or FDG-PET/CT nonprogression, but not both, while the median
progression-free survival was five months in patients with neither
< 5 CTCs nor FDG-PET/CT nonprogression.
“The multivariate analysis indicated that FDG-PET/ CT was the
only predictive sign,” De Giorgi and colleagues wrote. “However,
the combination of FDG-PET/CT and CTC might be a useful tool
to monitor response to therapy in patients without measurable
extraosseous disease, especially in patients with elevated CTC at
They also noted that the discordance of FDG-PET/CT assessment
and CTC count “needs to be evaluated in a prospective study to
determine the value of FDG-PET/CT and CTC individually and in
“A prospective study could validate the benefit of these two
approaches used separately and in combination in determining
prognosis, monitoring response, and establishing bone-dominant
disease as a tumor response-measurable disease,” they wrote.
F-18 fluoride PET/CT may offer one-stop shop for bone
[U.S. Food and Drug Administration] for clinical use and distribution,
so PET centers could make use of this useful test profitably.”
Skeletal PET gains support for pediatric bone scans
By Cynthia E. Keen staff writer
April 15, 2010
BOSTON - Skeletal scintigraphy with F-18 sodium fluoride (F-18
NaF) is a safe and effective way to diagnose skeletal disorders in
children and could be used instead of bone SPECT exams, according
to research presented on Wednesday at the Society for Pediatric
Radiology (SPR) meeting.
Skeletal PET bone imaging fell into disuse in the 1970s after SPECT
imaging with technetium sodium chloride was introduced, said Dr.
Frederick Grant of the division of nuclear medicine at Children’s
Hospital Boston. But tight supplies of technetium, caused by the
ongoing global shortage of molybdenum, have many nuclear imaging
specialists re-examining the technology.
Children’s Hospital Boston began to use F-18 NaF scintigraphy
routinely in 2005 and has had very positive experiences, Grant said.
In his SPR presentation, he reported results from a retrospective
study of 484 patients between infancy and 19 years of age who had
the procedure between April 2005 and March 2010, with skeletal
scintigraphy showing positive findings for 57%.
In the study, 87% of patients had the exam due to back pain -- often
due to sports injuries -- and, of these, 186 of 350 young athletes
had positive exam findings. Other indications included back pain
after trauma (13 patients with 54% positive findings), persistent
back pain after spinal fusion surgery (33 patients with 61% positive
findings), and metastatic disease. In most cases, images were of higher
resolution than with conventional SPECT, Grant said.
By Wayne Forrest staff writer
November 3, 2009
Monday, November 30 | 11:10 a.m.-11:20 a.m. | SSC09-05 | Room
Researchers from India will discuss a study that showed that PET/
CT with F-18 fluoride beat other nuclear medicine techniques for
detecting skeletal lesions, as well as for distinguishing between benign
and malignant tumors, in patients at high risk for skeletal metastases.
A total of 46 children younger than 2 who had indications of
nonaccidental trauma had positive findings 89% of the time. Grant
attributed this to selection bias, as these were patients suspected of
being victims of child abuse. Because of their very young age, these
children required sedation for the procedure.
Researchers at Tata Memorial Hospital in Parel, Mumbai, also found
that F-18 fluoride PET/CT had the least number of equivocal lesions
compared to technetium-99m methylene diphosphonate (MDP)
planar, SPECT, and SPECT/CT studies, due to the increased sensitivity
of fluoride over MDP and also due to the morphological detail
provided by CT.
For all patients, PET was performed 30 minutes after administration
of 21 MBq per kg (with a maximum of 148 MGq) F-18 NaF. Grant
recommended that patients be well hydrated. The imaging procedure
took 30 minutes or less, compared to 60 to 90 minutes for a technetium
bone SPECT exam, requiring an update period of up to three hours.
“The study provides enough evidence for the utilization of F-18
flouride PET/CT as a one-stop evaluation of bone metastases,” said Dr.
Venkatesh Rangarajan, lead author and professor in-charge of Tata’s
bioimaging unit. “The short duration of acquisition and the short
duration of the study is unique, and the [low] number of equivocal or
inconclusive findings makes this test significantly advantageous.”
“The shorter procedure time has improved department workflow, and
it enables us to obtain a higher utilization rate for the PET scanner,”
Grant said. “By educating medical doctors of large health insurance
companies, we also get reimbursement for this. The only payor
we haven’t had any success with is the Centers for Medicare and
Medicaid Services, because Medicare rules strictly apply to Medicaid
Given the current global shortage of molybdenum-99, Rangarajan
believes that shifting from bone scans to fluoride PET/CT studies
would be “a wise decision both for the patient and the doctor. F-18
flouride is a radiopharmaceutical which has been approved by the
Page 7
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Issue No.11 October 2010
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