Bioorganic & Medicinal Chemistry Letters 16 (2006) 5503–5506
Synthesis and biological evaluation of technetium-99m-labeled
deoxyglucose derivatives as imaging agents for tumor
Xiangji Chen, Liang Li, Fei Liu and Boli Liu*
Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry,
Beijing Normal University, Beijing 100875, PR China
Received 25 May 2006; revised 7 August 2006; accepted 9 August 2006
Available online 23 August 2006
Abstract—Three deoxyglucose (DG) derivatives, S-DG, MAG3-DG and MAMA-BA-DG, were synthesized and labeled successfully
with high labeling yields and high radio-chemical purities. Biodistribution in tumor-bearing mice demonstrated that these three new
99mTc-deoxyglucose derivatives showed accumulation in tumor and high tumor-to-muscle ratios. Among them, the 99mTc-MAG3-
DG showed the best characteristics as a potential tumor marker for single photon emission computed tomography (SPECT).
Ó 2006 Elsevier Ltd. All rights reserved.
Tumor is among the most common causes of death in
the world. In vivo functional imaging technique can help
to diagnose and stage tumors, optimize drug scheduling,
and predict response to a therapeutic modality, which
would be advantageous to both patient and oncologist.
showed similarities with [18F]FDG in tumor uptake.12
This suggests that there is feasibility for 99mTc-labeled
deoxyglucose as tumor metabolic imaging agents. How-
ever, [99mTc]ECDG still has some drawbacks such as
slow cleanup from blood, which would cause high blood
background; and large molecular weight, which would
limit its penetration through blood–brain barrier (BBB).
Flourine-18 (18F) fluorodeoxyglucose (FDG) has been
used to measure normal tissue and tumor glucose utili-
zation rates.1–5 Although tumor metabolic imaging with
[18F]FDG has been studied for more than two decades,
the use of this examination in clinical practice is still lim-
ited by such factors as difficult access, limited availabil-
ity, and high cost.6 In addition, positron emission
tomography (PET) radio-synthesis must be performed
rapidly because the half-life of F-18 is only 109 min.
Thus, it would be very desirable to develop less costly
imaging agents based on c-emitter isotope, especially
for developing country, where single photon emission
computed tomography (SPECT) is still dominant.
Thus, it would be desirable to develop a smaller 99mTc-
based deoxyglucose derivative with rapid blood clear-
ance and still maintaining its high tumor uptake.
The purpose of this study is to conjugate deoxyglucose
with different chelating agents and to evaluate the feasi-
bility of the 99mTc-labeled deoxyglucose derivatives as
candidates for tumor-imaging agents.
The 99mTc-S-DG was synthesized according to the pro-
cedure outlined in Scheme 1. After protecting the thiol
group of mercaptoacetic acid with trityl chloride, the
resulting compound 3 was reacted with glucosamine
using N,N0-dicyclohexyl-carbodiimide (DCC) as con-
densation reagent to obtain compound 4. Next, the thiol
groups were deprotected in trifluoroacetic acid (TFA) to
give 5. For labeling, 99mTc-S-DG was prepared by li-
gand-exchange reaction with 99mTc-glucoheptonate
(GH).
Technetium-99m (99mTc) has been mostly used for label-
ing radiopharmaceuticals owing to its suitable physical
and chemical characteristics and inexpensive isotope
cost. Lots of 99mTc-labeled glucose derivatives have been
synthesized in order to develop one subrogate in SPECT
for [18F]FDG in PET recently.7–11 Developed by Yang,
99mTc-labeled ethylenedicysteine-deoxyglucose (ECDG)
Synthesis of 99mTc-MAG3-DG (Scheme 2) was per-
formed from mercaptoacetic acid. After protecting the
thiol group with trityl chloride, the resulting compound
3 was reacted with N-hydroxysuccinimide (NHS) using
Keywords: Technetium; Deoxyglucose; Imaging agents.
*
Corresponding author. Tel./fax: +86 10 5880 8891; e-mail: liuboli@
0960-894X/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2006.08.050