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Evaluation of Radiolabeled Type IV Collagen Fragments as Potential Tumor Imaging Agents

Summary: Evaluation of Radiolabeled Type IV Collagen Fragments as
Potential Tumor Imaging Agents
W. Barry Edwards, Carolyn J. Anderson,* Gregg B. Fields,
and Michael J. Welch
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63110 and
Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, Florida 33431.
Received June 26, 2001; Revised Manuscript Received September 18, 2001
The objective of this study was to examine radiopharmaceuticals that target the R3 1 integrin to
determine if these agents target tumors for diagnostic imaging and/or targeted radiotherapy of cancer.
Prior studies had shown that residues 531-542 from the R1 chain of type IV collagen bind a variety
of tumor cell R3 1 integrins. A peptide mimic of this sequence containing all D-amino acids (designated
D-Hep-III) was synthesized by solid-phase methods. The tetraazamacrocyclic chelator, TETA, was
conjugated to the peptide while it was resin-bound. TETA-D-Hep-III and D-Hep-III were radiolabeled
with 64
Cu and 125
I, respectively, in high specific activity and radiochemical purity. Heterologous
competitive binding assays between D-Hep-III and either 125I-D-Hep-III or 64Cu-TETA-D-Hep-III
indicated low micromolar affinity of D-Hep-III. The biodistribution of each radiolabeled analogue of
D-Hep-III was carried out in rats and tumor-bearing mice. Both analogues were rapidly cleared from
the blood in normal rats, with the kidneys receiving the highest accumulation of each. SKOV3 human


Source: Anderson, Carolyn J. - Department of Molecular Biology and Pharmacology, Washington University in St. Louis


Collections: Biology and Medicine