Evidence of specificity of radiolabeled phage display peptides for the TAG-72 antigen.
The TAG-72 glycoprotein is highly expressed in many tumor types and has been considered a target for tumor imaging. In this work, we used the f88-4/Cys6 phage library of constrained 16 mer peptides to select those that demonstrate binding to TAG-72. Three consensus peptides were identified: NPGTCKD-KWIECLLNG (clone A); NLIWCRKEFARCTSDM (clone B); and LKNYCRKCSNRCTPTG (clone C). The phage of clones containing these peptides were radiolabeled with technetium-99m (99mTC) at 90% radiochemical purity and were incubated with TAG-72-positive LS174T colon cancer cells. The phage of clones A and B bound significantly higher by 4.5-fold and 1.5-fold than that of a nonspecific control phage. The 99mTc-labeled phage of clones A, B, and control were also administered intravenously to mice with LS-174T tumors. The accumulation of phages from clone A showed a slightly statistically higher accumulation in the tumor (0.51% ID/g), compared to phages of clone B and control phage (0.28% and 0.29% ID/g; p=0.049 for both). In conclusion, the peptide expressed by clone A phage showed evidence of significant specific binding when presented as the radiolabeled phage to tumor in vivo and especially in vitro with cells and solid tumor. The results suggest that this peptide when free of the phage may have potential for the imaging and possibly radiotherapy of TAG-72-expressing cancers.
Rusckowski
Mary
M
Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655-0243, USA. mary.rusckowski@umassmed.edu
Gupta
Suresh
S
Liu
Guozheng
G
Dou
Shuping
S
Hnatowich
Donald J
DJ
D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D006023:Glycoproteins / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051379:Mice; D019151:Peptide Library; D010455:Peptides / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D012680:Sensitivity and Specificity; D013667:Technetium / Q000032:analysis* / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays