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M O L E C U L A R O N C O L O G Y 4 ( 2 0 1 0 ) 1 1 9 – 1 2 5
ava i lab le at www.sc ienced i rec t . com
www.e lsev ie r . com/ loca te /molonc
Positron emission tomography imaging of DMBA/TPA mouse skin
multi-step tumorigenesis
Tomo-o Ishikawaa, Indracanti Prem Kumara, Hidevaldo B. Machadoa, Koon-Pong Wonga,Donna Kusewittb, Sung-Cheng Huanga, Susan M. Fischerb, Harvey R. Herschmana,c,*aDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USAbThe University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USAcDepartment of Biological Chemistry, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA
A R T I C L E I N F O
Article history:
Received 15 January 2010
Received in revised form
23 January 2010
Accepted 24 January 2010
Available online 2 February 2010
Keywords:
Glucose metabolism
PET
Skin cancer
Molecular imaging
Fluorodeoxyglucose
* Corresponding author at: 341 Boyer Hall, Ufax: þ1 310 825 1447.
E-mail address: [email protected]/$ – see front matter ª 2010 Federdoi:10.1016/j.molonc.2010.01.005
A B S T R A C T
Many tumor cells have elevated rates of glucose uptake that can be measured quantita-
tively, noninvasively and repeatedly by positron emission tomography (PET) with 2-de-
oxy-2-[18F]-fluoro-D-glucose (18F-FDG). Clinical imaging with 18F-FDG PET has been used
for detection and staging of primary and metastatic tumors. High-resolution microPET
scanning and murine cancer models make it possible to analyze longitudinally glucose me-
tabolism during the appearance, development and progression of individual experimental
tumors. In this study, we used 18F-FDG microPET and micro computerized tomography (mi-
croCT) to investigate glucose uptake in the DMBA/TPA chemically-induced multistage
mouse skin carcinogenesis model. 18F-FDG uptake is significantly higher in all papillomas
than in surrounding skin. Elevated 18F-FDG uptake is observed when tumors can be iden-
tified morphologically, but not before. Although 18F-FDG uptake is high in all fully invasive,
malignant skin squamous cell carcinomas, uptake in papillomas and microinvasive malig-
nant squamous cell carcinomas is variable and does not exhibit any correlation with tumor
stage.
ª 2010 Federation of European Biochemical Societies.
Published by Elsevier B.V. All rights reserved.
1. Introduction measured with 18F-FDG PET is largely dependent on the rate
Positron emission tomography (PET) with the glucose ana-
logue 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) positron-
emitting tracer is a widely used clinical imaging technique
to detect primary and metastatic cancers (Phelps, 2000). Nu-
merous 18F-FDG PET studies have demonstrated that most
malignant human tumors show significantly increased 18F-
FDG uptake. Elevated rates of 18F-FDG uptake are also strongly
correlated with poor outcome in many cancers (Gambhir
et al., 2001; Kelloff et al., 2005). The increased tracer uptake
CLA, 611 Charles E. Youn
la.edu (H.R. Herschman).ation of European Bioche
of glycolysis. Injected 18F-FDG is transported through the cell
membrane by glucose transporters and then phosphorylated
by hexokinase to 18F-FDG-6-phosphate. Because 18F-FDG-6-
phosphate cannot be metabolized, and the cell membrane is
not permeable for phosphorylated 18F-FDG, 18F-FDG-6-phos-
phate is trapped and accumulates in cells. When the unphos-
phorylated 18F-FDG has been eliminated from tissues and
blood, from tissues and blood, the accumulation of phosphor-
ylated 18F-FDG can be imaged and quantitatively measured by
PET scanning (Phelps, 2000).
g Drive East, Los Angeles, CA 90095, USA. Tel.: þ1 310 825 8735;
mical Societies. Published by Elsevier B.V. All rights reserved.
M O L E C U L A R O N C O L O G Y 4 ( 2 0 1 0 ) 1 1 9 – 1 2 5120
With the development of high-resolution microPET scan-
ners designed for laboratory animal imaging, the pre-clinical
application of non-invasive imaging of animal models has in-
creased substantially (Herschman, 2003). In vivo imaging of
mouse models of cancer makes it possible to analyze – non-
invasively, quantitatively and repeatedly – the longitudinal
development and progression of individual tumors (Cherry,
2001). Xenograft models of human tumors on immunocom-
promised mice have been widely used for this purpose; how-
ever, several crucial differences exist for such models when
compared either to endogenous tumors in patients or to au-
tochthonous murine tumors. Such differences include, but
are not limited to, tumor architecture, microenvironment, im-
mune modulation and cell autonomous features (Frese and
Tuveson, 2007). In contrast, chemically-induced murine can-
cers in immunocompetent mice are widely used as autoch-
thonous preclinical cancer models in which to study genetic
effects, the role of microenvironment, immune modulation
and alternative therapeutic approaches.
One of the most intensively studied chemically-induced
cancer models is the murine skin carcinogenesis model
(Kemp, 2005). This model exemplifies the three stages of
tumor development; initiation, promotion and progression.
Initiation is generally elicited by the application of a low
dose of carcinogen such as 7,12-dimethylbenz[a]anthracene
(DMBA). This treatment causes an activating, oncogenic mu-
tation of the H-ras gene in skin epithelial cells. Those cells
are promoted by repeated application of a non-carcinogenic
promoter such as 12-0-tetradecanoylphorbol-13-acetate
(TPA). Tumor promoters do not directly change the DNA
sequence, however, they elicit a wide range of cellular and
biochemical changes related to cell growth and differentia-
tion. Initiated cells are expanded by promoter treatment
and develop into premalignant papillomas. The progression
step in DMBA/TPA induced skin cancer is a spontaneous
process facilitated by genetic instability; loss of p53 gene is
frequent. Some papillomas acquire the ability to invade as
a result of the progression step and become squamous cell
carcinomas (SCCs). The DMBA/TPA induced multi-stage car-
cinogenesis model has been used to test many hypotheses
in cancer biology, prevention and treatment of cancer
(Abel et al., 2009).
In this study, we used 18F-FDG microPET and microCT
analyses to monitor tumor metabolism longitudinally
during tumor development induced by DMBA/TPA. We
then assessed the relationship between 18F-FDG uptake in
papillomas and the subsequent fate of the tumors, to deter-
mine if microPET analysis of papillomas can predict papil-
loma fate.
2. Materials and methods
2.1. Mice and materials
Female FVB/N mice were purchased from Charles River Labo-
ratory (Wilmington, MA). Animal experiments were carried
out with Animal Research Committee approval at UCLA.
DMBA and TPA were purchased from Sigma (St. Louis, MO).
2.2. Tumor experiments
Mice were shaved on the dorsal skin area. Two days after
shaving, they were treated topically with 100 mg of DMBA in
200 ml of acetone. One week after initiation, the mice were
treated with 2.5 mg of TPA in 200 ml acetone once a week until
the end of the experiment.
2.3. Positron emission tomography/computedtomography imaging
Positron emission tomography (PET)/computed tomography
(CT) scans were performed with a microPET FOCUS 220 PET
scanner (Siemens Preclinical Solutions, Malvern, PA) and
a MicroCAT II CT scanner (Siemens Preclinical Solutions). Re-
peated microPET and microCT images were taken before re-
peated TPA treatments. The mice were injected i.p. with
approximately 200 mCi/mouse of 18F-FDG, anesthetized with
2% isoflurane and kept, under anesthesia, at 34�C during
tracer uptake and during subsequent microPET and microCT
imaging analyses. After 1 hour uptake of 18F-FDG tracer,
microPET images were taken for 10 min, followed by micro-
CAT scans for 7 min. MicroPET images were reconstructed us-
ing a three-dimensional filtered back-projection
reconstruction algorithm and were aligned with the microCT
image using software provided by the vendor. A maximum
a posteriori reconstruction protocol was used for presentation
of images. The images were displayed and analyzed with AM-
IDE software (Loening and Gambhir, 2003). Tumor 18F-FDG up-
take was determined by a three dimensional region of interest
(ROI) analysis and normalized by the 18F-FDG uptake in the
brain (Abbey et al., 2006); consequently the 18F-FDG uptake
values reported in the Results are unitless.
2.4. Tumor grading
After mice were euthanized, tumors were harvested for histo-
logic grading. Hematoxylin-eosin stained tumor tissue sec-
tions were graded in a blinded manner by a board certified
veterinary pathologist. Tumors were graded as papilloma
(grades 1–3), microinvasive squamous cell carcinoma (grades
1–3), or fully invasive squamous cell carcinoma (Thomas-
Ahner et al., 2007) and defined as follows: papillomas are exo-
phytic tumors that show no evidence of stromal invasion.
Squamous cell carcinomas have a more endophytic appear-
ance, with stromal invasion evidenced by loss of basement
membrane continuity and development of an inflammatory
stromal response. A grade 1 papilloma is composed primarily
of epithelium without a pronounced papillary pattern. A grade
2 papilloma is a well-differentiated papillary mass. A grade 3
papilloma is similar to a grade 2 papilloma, except that
a few finger-like projections of atypical cells at the base of
the mass are present. Microinvasive squamous cell carcino-
mas are subcategorized by depth of penetration into the der-
mis. Only tumors that invaded the panniculus carnosus were
classified as fully invasive squamous cell carcinomas. All
grades of papillomas were considered premalignant. Squa-
mous cell carcinoma and all grades of microinvasive squa-
mous cell carcinoma were considered malignant.
M O L E C U L A R O N C O L O G Y 4 ( 2 0 1 0 ) 1 1 9 – 1 2 5 121
3. Results
In the DMBA/TPA induced skin cancer model conversion of
premalignant papillomas to malignant squamous cell carci-
nomas generally occurs at a low rate. However, this rate varies
among murine strains. To obtain an analyzable number of
malignant tumors FVB/N mice, which are highly susceptible
for SCC development because of a polymorphism in the
Patched gene (Hennings et al., 1993; Wakabayashi et al.,
2007), were used in this study.18F-FDG microPET/microCT imaging was performed for
eight FVB/N mice on which skin tumors were induced by
DMBA/TPA treatment. Initial photographic images and 18F-
FDG microPET/microCT images were begun between 11–14
weeks after DMBA treatment, when tumors on each mouse
can be clearly distinguished; successive images from one
mouse are shown in Figure 1. Imaging was repeated at two-
week intervals and continued up to 15–24 weeks, until total tu-
mor burden reached the maximal size permitted for the ap-
proved protocol. After the last image, mice were euthanized
and tumors were processed for histological examination
(Figure 2).
A total of 61 tumors from the eight DMBA/TPA treated mice
were analyzed for 18F-FDG uptake and histology. A three-
Figure 1 – Example longitudinal imaging of developing DMBA/TPA induce
times after DMBA treatment (lower panels). To show the signal from skin
masked. Photos were taken at the same times (upper panels). Correspondin
scale indicates uptake relative to brain, with red being the highest, and lower
the 18F-FDG concentration in brain.
dimensional ROI for each tumor was defined, based on
microCT images. The maximal uptake value in each three-
dimensional ROI was used to evaluate tumor 18F-FDG uptake.
To examine a possible correlation between 18F-FDG uptake
and tumor stage, tumor 18F-FDG uptake values at the last time
point prior to sacrifice were compared with histologic tumor
grades (Figure 3A). All fully invasive SCCs show 18F-FDG up-
take greater than 1.8; in addition, the average value for fully
invasive SCC 18F-FDG uptake is significantly higher than that
of other tumor grades (P< 0.01 by unpaired t-test).
Invasion beyond the basement membrane is the hallmark
that distinguishes malignant from premalignant tumors in
this skin tumor paradigm (Kemp, 2005; Abel et al., 2009). In
this histological view, microinvasive tumors are also consid-
ered to be malignant. However, the average 18F-FDG uptake
value for microinvasive tumors is similar to the average 18F-
FDG uptake value for premalignant papillomas rather than
to the average 18F-FDG uptake value for fully invasive SCCs
(Figure 3A); average 18F-FDG uptake values for microinvasive
tumors and papillomas are not significantly different from
one another. Moreover, premalignant papillomas and micro-
invasive tumors show great variability of 18F-FDG uptake;
some individual papillomas and microinvasive tumors have18F-FDG values within the range observed for SCCs. Thus there
is no clear 18F-FDG value that can distinguish between
d skin tumors. 18F-FDG PET/CT images were taken at the indicated
tumor in two dimensional images, signals from internal organs are
g tumors are indicated by numbered arrows in each panel. The color
values in yellow, green and blue. Signal intensities were normalized to
Figure 2 – Representative histological views of DMBA/TPA induced skin tumor types. Tumors were harvested after the last imaging time points
and processed for hematoxylin-eosin staining. (A) Papilloma, grade 1–2. (B) Papilloma, grade 3. (C) Microinvasive squamous cell carcinoma, grade 1.
(D) Microinvasive squamous cell carcinoma, grade 2. (No microinvasive squamous cell carcinomas, grade 3, were observed). (E) Fully invasive
squamous cell carcinoma.
M O L E C U L A R O N C O L O G Y 4 ( 2 0 1 0 ) 1 1 9 – 1 2 5122
premalignant and malignant tumors in the DMBA/TPA tumor-
igenesis model. Tumor 18F-FDG uptake was also compared
with 18F-FDG uptake in normal skin. Average 18F-FDG uptake
for all tumor classes is significantly higher than that of normal
skin (Figure 3A).
We also analyzed 18F-FDG uptake as a function of tumor
volume, at the last time point prior to euthanasia, for these
sixty-one tumors (Figure 3B). All fully invasive SCCs show
3
2
1
0normal
skinpap1-2
pap3
MI1
MI2 SCC
max
FD
G u
ptak
e
A B
Figure 3 – 18F-FDG uptake in each tumor shortly before mice were eutha
(A) Maximum uptake values of 18F-FDG for normal skin (without tumor) a
of each group is shown as a horizontal bar. (B) Maximum 18F-FDG uptake
grade 1–2 papillomas, pap 1–2; grade 3 papillomas, pap 3; grade 1 microinva
cell carcinomas, MI2; and fully invasive squamous cell carcinomas, SCC.
significantly greater size along with higher 18F-FDG uptake.
However, for other tumor grades, including malignant micro-
invasive tumors, there is no correlation between tumor size
and 18F-FDG uptake.
At the last time point, immediately before tumors were
evaluated histologically, all SCCs were significantly larger
than any other tumor (Figure 3B). Early growth rates for papil-
lomas destined to become SCCs were similar to the growth
pap 1-2pap 3MI 1MI 2SCC
0 200 400 600 800 1000
3
2
1
0
max
FD
G u
ptak
e
tumor size (mm3)
nized and tumors were processed for histological examination.
nd for each tumor, for various tumor histological grades. The average
values for each tumor, plotted versus tumor volume. Symbols identify
sive squamous cell carcinomas, MI1; grade 2 microinvasive squamous
10 12 14 16 18 20 22weeks
1000
800
600
400
200
0
tum
or s
ize
(mm
3 )
10 12 14 16 18 20 22weeks
3
2
1
0
max
FD
G u
ptak
e
BA
Figure 4 – (A) Estimated volume by CT of fully invasive squamous cell carcinomas (red lines) and representative papillomas (blue lines).
(B) Maximum uptake of 18F-FDG of the tumors shown in (A).
M O L E C U L A R O N C O L O G Y 4 ( 2 0 1 0 ) 1 1 9 – 1 2 5 123
rates of papillomas that did not progress to SCCs (Figure 4A).
Papillomas that subsequently progressed to SCCs then dem-
onstrate a more rapid growth rate.
We utilized the advantage of longitudinal, non-invasive,
repeated microPET imaging to determine whether patterns
of 18F-FDG uptake during the progression period of papillomas
that subsequently become SCCs are distinguishable from 18F-
FDG uptake patterns of papillomas that do not progress to
SCCs (Figure 4B). The transition to tumors that will become
SCCs is not correlated with a distinctive pattern of 18F-FDG up-
take during the papilloma stage; transition to a SCC commit-
ted path cannot be predicted from the pattern of 18F-FDG
uptake during the promotion or progression stages of DMBA/
TPA induced carcinogenesis (Figure 4B).
In a separate analysis of three of the tumor bearing mice
that were subjected to six microPET/microCT scans at two
week intervals (weeks 14–24), a comparison of the slopes of
the normalized maximum %ID/g of tumors that remained as
papillomas (grades 1–3, PAP1-3) versus the normalized maxi-
mum %ID/g of papillomas destined to become either microin-
vasive squamous cell carcinomas (grades 1 and 2) or fully
invasive squamous cell carcinomas (normalized to muscle,
MI/SCC) was performed, to see if this alternative analysis in
10 12 14 16 18 20 22weeks
0
160
120
80
40tum
or s
ize
(mm
3 )
BA
Figure 5 – Comparison of tumor volume (A) and maximum
mice where tumor burden permitted a greater number of im-
aging sessions could distinguish between tumors that
remained as premalignant papillomas and tumors that pro-
gressed to carcinomas. This analysis also failed to distinguish
tumors that were classified as PAP1-3 premalignant tumors at
the conclusion of the experiment from those that had pro-
gressed to MI/SCC (P> 0.05; data not shown). Linear discrimi-
nant analysis was also not able to distinguish between
papillomas destined to become malignant MI/SCC tumors
and papillomas that did not progress; correct classification ac-
curacy was only about 60% (cross validated; 56%), depending
on the choices of predictor variables.
In this tumorigenesis model papillomas either progress to
malignant SCCs, remain as premalignant tumors, or regress
in size. To evaluate whether the 18F-FDG uptake predicts
and/or correlates with reduction in tumor size, we once again
utilized the advantage of non-invasive, longitudinal, repeated
microPET imaging to monitor 18F-FDG uptake in papillomas
that decreased in size, and compared FDG uptake with size
change (Figure 5). There is no characteristic change of 18F-
FDG uptake before tumors regress in size.
Finally, we investigated whether 18F-FDG uptake is sensi-
tive enough to indicate the location of an emerging tumor
10 12 14 16 18 20 22weeks
0
1.6
1.2
0.8
0.4max
FD
G u
ptak
e
uptake of 18F-FDG (B) in regressing tumors in size.
–1 0 +10
Weeks
FDG
upt
ake
0.2
0.4
0.6
0.8
*
Figure 6 – 18F-FDG uptake in emerging tumors. Maximum 18F-FDG
uptake was determined on ROIs placed over the tumor area using the
CT image as reference, one week before (week L1) and after (week
D1) the tumor was initially clearly defined on the CT scan (week 0).
Data are normalized to brain 18F-FDG uptake and are expressed as
means ± s.d. (n [ 6). * P < 0.05, one-way ANOVA followed by
Bonferroni test.
M O L E C U L A R O N C O L O G Y 4 ( 2 0 1 0 ) 1 1 9 – 1 2 5124
before the tumor is morphologically detectable. To answer
this question, the 18F-FDG uptake values for 6 tumors (on
two mice) were compared at one week prior to and one
week after the tumors were clearly defined by CT scan
(1 mm diameter). 18F-FDG uptake values observed when the
tumors are first clearly distinguishable by microCT analysis
(week ‘‘0’’ in Figure 6) are not significantly different from the
values observed at the same sites one week earlier. In the
DMBA/TPA skin tumor model 18F-FDG uptake is not able to
predict the emergence of a tumor prior to morphological/
structural appearance of the tumor.
4. Discussion
Many tumors, in contrast to their normal cells of origin, use
aerobic glycolysis (the Warburg effect) and have elevated rates
of glucose uptake (Vander Heiden et al., 2009). Consequently,
imaging of tumor glucose metabolism with 18F-FDG PET can,
in many cases, differentiate malignant tissue from benign le-
sions in human patients (Phelps, 2000). The use of microPET,
an imaging system developed for small animals, provides an
opportunity to analyze tumor glucose metabolism in murine
disease models (Herschman, 2003).
Tumorigenesis is a multistep process that involves a se-
ries of genetic and epigenetic alterations, e.g., dominant on-
cogene activation and tumor-suppressor gene inactivation.
The accumulated mutations change the behavior of cells
from normal growth control to unrestricted growth, leading
to malignancy, invasion into surrounding tissues, and me-
tastasis. The DMBA/TPA mouse skin carcinogenesis model
establishes links between genetic and biochemical pathways
of initiation, promotion and progression with histological
stages of tumor development (Kemp, 2005). Histology is
the gold standard for assessing the malignancy status of
these tumors. In this study, we assessed 18F-FDG uptake in
the DMBA/TPA induced mouse skin carcinogenesis model.
We find that elevated 18F-FDG uptake, detectable by micro-
PET analysis, is present in all tumors when papillomas are
morphologically identifiable. However, by analyzing the re-
lationship between tumor malignancy and 18F-FDG uptake,
we find that 18F-FDG uptake is not correlated with tumor
malignancy; no clearly distinguishable threshold 18F-FDG
value or pattern of 18F-FDG uptake in tumors progressing
to malignancy can distinguish premalignant from malignant
tumors.
In DMBA/TPA carcinogenesis, repeated TPA treatment
causes skin hyperplasia. These hyperplastic, but preneo-
plastic, lesions do not exhibit substantially elevated18F-FDG uptake. In contrast, significantly elevated 18F-FDG
uptake is observed in all tumors; premalignant papillomas
can be clearly distinguished from normal skin and from
preneoplastic regions. DMBA/TPA skin tumor induction is
nearly always initiated by an oncogenic H-ras mutation
(Quintanilla et al., 1986). The initiated cell, with an H-ras
mutation, is ‘‘promoted’’ by repeated TPA treatment to ex-
pand into a papilloma. Ras activation is implicated in regu-
lation of aerobic glycolysis (Gillies et al., 2008). For example,
oncogenic H-ras stimulates glycolysis and inhibits oxygen
consumption in rat embryo cells (Biaglow et al., 1997) and
inhibition of H-ras resulted in diminished glycolysis and
cell death in glioblastoma cells (Blum et al., 2005). Our
data suggest that activating mutations in H-ras could con-
tribute to the higher 18F-FDG uptake we observe in all pap-
illomas. However, elevated 18F-FDG uptake is not detected
before tumors are identified morphologically by microCT,
although cells with activated H-ras genes must be present.
Our inability to detect these cells may be due to the finite
spatial resolution of microPET imaging; the ability to detect
affected tissues whose volumes are substantially smaller
than the size corresponding to the imaging spatial resolu-
tion may limit the sensitivity of the microPET assay. Alter-
natively, additional biological events could be required for
elevated 18F-FDG uptake after tumors are visible.
In SCCs, loss of heterozygosity and/or mutation of the p53
gene occurs frequently (Kemp, 2005). Wild-type p53 plays
a key role in regulating glycolysis and glucose consumption
(Kondoh et al., 2005; Bensaad and Vousden, 2007). All fully inva-
sive SCCs in this study show elevated 18F-FDG. However, vari-
able and, in some cases, high 18F-FDG uptake – as great as
that observed in SCCs – is also observed in some papillomas.
It is unlikely that these papillomas, which did not progress to
SCCs, would have p53 mutations. This complex pattern of ele-
vated 18F-FDG uptake in papillomas, microinvasive SCCs and
fully invasive SCCs in the DMBA/TPA skin multistep tumori-
genesis model is consistent with the view that ‘‘the altered ex-
pression of classical cancer-related genes cannot be the only
explanation for the development and maintenance of the aber-
rant glycolytic phenotype of cancer cells’’ (Ortega et al., 2009).
The relationship between 18F-FDG uptake and tumor grade
may differ for cancers of differing origins and types. In human
tumors, a relatively strong correlation was reported in gliomas
and sarcomas, however several benign or borderline malig-
nant tumors demonstrated intense 18F-FDG uptake (Buerkle
and Weber, 2008). Increased 18F-FDG uptake before transition
M O L E C U L A R O N C O L O G Y 4 ( 2 0 1 0 ) 1 1 9 – 1 2 5 125
to an invasive phenotype also occurs in a mouse syngeneic
mammary tumor engraftment model (Abbey et al., 2004).
Although DMBA/TPA induced papillomas may progress to
invasive malignant carcinomas, most papillomas follow dif-
ferent fates. Some papillomas grow without progression to
malignancy. Other papillomas stay the same size, while still
other papillomas regress in size. Because alterations in glu-
cose metabolism might precede and predict alterations in tu-
mor cell proliferation, we analyzed longitudinal 18F-FDG
uptake in papillomas that regressed in size. However, prior18F-FDG uptake is unable to predict subsequent reduction in
papilloma size; 18F-FDG uptake during early tumor prolifera-
tion is not a good surrogate marker to predict the fate of pap-
illomas in DMBA/TPA skin tumorigenesis.
In conclusion, elevated 18F-FDG uptake is observed in all
DMBA-TPA induced skin tumors, when they are identifiable
morphologically by eye or by microCT, but not before. Although18F-FDG uptake is high in all malignant fully invasive SCCs, the
level of 18F-FDG uptake in individual pre-malignant papillomas
is not informative with regard to their subsequent fate.
Acknowledgements
We thank Arthur Catapang and the members of the UCLA Small
Animal Imaging Shared Resource for technical assistance.
These studies were supported by NIH awards R01 CA084572,
R01 CA 123055 and P50 CA086306 to HRH, and CA100140 to SF.
IPK was supported by an overseas associateship from the De-
partment of Biotechnology, Government of India.
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