Radiolabeled somatostatin analogues are being developed as cancer imaging and radiotherapy agents to target somatostatin receptor-positive tumors. The overall goal of this proposal is to synthesize, characterize and evaluate Tc-99m- and Re-188-cyclized somatostatin peptide derivatives for diagnostic imaging and targeted radiotherapy, respectively, of cancer. The hypothesis to be addressed is that structural modification of somatostatin analogues to increase retention of radioactivity in tumors will result in both improved tumor imaging contrast and more effective therapy at lower doses that would spare the non-target tissues. The objectives of this proposal, in brief, are (1) to synthesize and characterize somatostatin receptor-targeting peptides with non-radioactive Re, Re-188, Tc-99m and Tc-99 incorporated directly into the peptide disulfide bond; (2) to correlate the in vitro receptor binding affinities of the Re and Tc-99 complexes to their three dimensional solution phase structures; (3) to evaluate the in vivo distributions and tumor-targeting properties of the Tc-99m- and Re-188-cyclized peptides with high receptor binding; and (4) to assess the radiotherapeutic potential of the optimal Re-188-coordinated peptide in a mouse model of pancreatic cancer. ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA119894-03
Application #
7435411
Study Section
Special Emphasis Panel (ZRG1-SBIB-H (20))
Program Officer
Silkensen, Shannon M
Project Start
2006-07-01
Project End
2009-07-31
Budget Start
2008-07-01
Budget End
2009-07-31
Support Year
3
Fiscal Year
2008
Total Cost
$52,048
Indirect Cost
Name
University of Missouri-Columbia
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
153890272
City
Columbia
State
MO
Country
United States
Zip Code
65211
Bigott-Hennkens, Heather M; Dannoon, Shorouk F; Noll, Samantha M et al. (2011) Labeling, stability and biodistribution studies of 99mTc-cyclized Tyr3-octreotate derivatives. Nucl Med Biol 38:549-55
Dannoon, Shorouk F; Bigott-Hennkens, Heather M; Ma, Lixin et al. (2010) In vitro structure-activity relationship of Re-cyclized octreotide analogues. Nucl Med Biol 37:527-37
Bigott-Hennkens, H M; Dannoon, S; Lewis, M R et al. (2008) In vitro receptor binding assays: general methods and considerations. Q J Nucl Med Mol Imaging 52:245-53
Bigott-Hennkens, Heather M; Junnotula, Sulochana; Ma, Lixin et al. (2008) Synthesis and in vitro evaluation of a rhenium-cyclized somatostatin derivative series. J Med Chem 51:1223-30