1250
X. Fei et al. / Bioorg. Med. Chem. Lett. 14 (2004) 1247–1251
(CCEMH) pilot and feasibility (P/F) grant (to Q.H.Z.),
the National Institutes of Health/National Cancer
Institute grant P20CA86350 (to G.D.H.), the Indiana
21st Century Research and Technology Fund (to
G.D.H.), and the Lilly Endowment Inc. to Indiana
Genomics Initiative (INGEN) of Indiana University.
We thank Dr. Bruce Mock, Barbara Glick-Wilson and
Michael Sullivan for the efforts in producing carbon-11
precursors and [18F]fluoride. The IL-1a transfected cells
were a kind gift of Dr. Harikrishna Nakshatri. The
referees’ criticisms and editor’s comments for the revi-
sion of the manuscript are greatly appreciated.
References and notes
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Figure 2. Micro-PET image of [11C]T138067 in a MDA-MB-435
implanted athymic mouse.
min post iv injection of 1 mCi of the tracer. The images
are shown in Figures 1 and 2. The tumor area in the
tumor-bearing mouse was pointed out by the arrow in
the Figures. Both MCF-7 transfected with IL-1a tumor
and MDA-MB-435 tumor were not visible with the tra-
cer [11C]T138067 as clearly shown in the in vivo micro-
PET images.
In summary, the synthetic procedures that provide radi-
olabeled antimitotic agents [11C]T138067 and [18F]T138067
have been developed. From the in vivo study results, we
concluded that while in vitro experiments indicate effi-
cacy of antimitotic drug T138067,2 kinetic factors and
rapid blood clearance26 make [11C]T138067 unsuitable
as tracer for nuclear medicine imaging of tubulin poly-
merization. Based on the results of [11C]T138067, we
may suggest both [11C]T138067 and [18F]T138067 will
not be suitable as PET cancer imaging agents. This type
of work regards simply radiolabeling a drug that has
been developed for therapeutic purposes as is the case
with T138067 which is in phase II clinical trials indicates
that successful drugs for therapeutic and imaging pur-
poses almost invariably demonstrate different pharma-
cokinetic profiles to each other and by far the largest
majority of useful imaging agents would not be useful in
therapy.
12. Zheng, Q.-H.; Liu, X.; Fei, X.; Wang, J.-Q.; Ohannesian,
D. W.; Erickson, L. C.; Stone, K. L.; Martinez, T. D.;
Miller, K. D.; Hutchins, G. D. J. Labelled Cpd. Radio-
pharm. 2002, 45, 1239.
Acknowledgements
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15. Zheng, Q.-H.; Wang, J.-Q.; Fei, X.; Hutchins, G. D.
Synthesis 2003, 2785.
This work was partially supported by the Susan G.
Komen Breast Cancer Foundation grant IMG 02-1550
(to Q.H.Z.), the Indiana University American Cancer
Society (ACS) Institutional Grant Committee grant
IRG-84-002-17 (to Q.H.Z.), the Indiana University
Cores Centers of Excellence in Molecular Hematology
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