Design of a Tetravalent RGD Peptide Capable of Simultaneous Binding with Multiple Integrin αvβ3 for Targeted Radionuclide Therapy

For
targeted radionuclide therapy, radioligands that exhibit high
and persistent tumor uptake are indispensable. We previously synthesized
a 99mTc-labeled hexavalent RGD peptide (99mTc-(RGD)6) as a tumor imaging agent targeting integrin αvβ3. 99mTc-(RGD)6 showed high in vivo tumor uptake with
long retention due to simultaneous binding to multiple integrin αvβ3
receptors. The purpose of this study was to apply this finding to
the design of a multivalent RGD peptide labeled with 211At, a promising α-emitting radionuclide for radionuclide therapy.
As a candidate compound, a tetravalent RGD peptide (H2N-(RGD)4) was synthesized and radiolabeled with 125I, a
homologous element of At, for basic studies. As expected, 125I-(RGD)4 retained the capability of simultaneous binding
and showed comparable in vivo tumor uptake to 99mTc-(RGD)6. Finally, 211At-(RGD)4 was synthesized
with >95% radiochemical purity and exhibited an almost identical
biodistribution
pattern to 125I-(RGD)4. These results indicate
that 211At-(RGD)4 might be a potential radioligand
for integrin αvβ3-targeted radionuclide therapy.