Pharmacokinetics and tumor retention of 125I-labeled RGD peptide are improved by PEGylation.

Tumor growth and metastasis are angiogenesis dependent. Overexpression of integrin alphavbeta3 in angiogenic vessels as well as various malignant human tumors suggests the potential of suitably labeled antagonists of this adhesion receptor for radionuclide imaging and therapy of tumors. Small head-to-tail cyclic peptides including the Arg-Gly-Asp (RGD) amino acid sequence have been radiolabeled and studied in preclinical animal models. However, the fast blood clearance, high kidney and liver uptake, and rapid washout from tumors make this type of tracer ineffective for clinical applications. In this study we modified the cyclic pentapeptide c(RGDyK) with monofunctional methoxy-PEG (mPEG, M.W. = 2,000) and labeled the RGD-mPEG conjugate with 125I. We studied the tumor targeting efficacy and in vivo pharmacokinetic properties of 125I-RGD-mPEG by means of direct tissue sampling and autoradiography in mice xenografted subcutaneously with U87MG glioblastoma. Compared to the 125I-RGD analog, this PEGylated RGD peptide revealed faster blood clearance, lower kidney uptake, and prolonged tumor uptake without compromising the receptor targeting ability.