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The Quarterly Journal of Nuclear Medicine and Molecular Imaging 2007 March;51(1):33-41


language: English

Comparison of in vitro and in vivo properties of [99mTc]cRGD peptides labeled using different novel Tc-cores

Decristoforo C. 1, Santos I. 2, Pietzsch H. J. 3, Kuenstler J. U. 3, Duatti A. 4, Smith C. J. 5, Rey A. 6, Alberto R. 7, Von Guggenberg E. 1, Haubner R. 1

1 Department of Nuclear Medicine Medical University of Innsbruck, Innsbruck, Austria 2 Inorganic and Radiopharmaceutical Group Technologic and Nuclear Institute, Sacavém, Portugal 3 Institute for Radiopharmacy, FZR Rossendorf, Germany 4 Laboratory of Nuclear Medicine University of Ferrara, Ferrara, Italy 5 Department of Radiology and MURR University of Missouri and the HSTMVH, Columbia, MO, USA 6 Radiochemistry Laboratory, Faculty of Chemistry University of the Republic, Montvideo, Uruguay 7 Institute of Inorganic Chemistry University of Zurich, Zurich, Switzerland


Aim. The αvβ3 integrin is involved in angiogenesis and tumor metastasis. Arginine-glycine-aspartic acid (RGD)-peptides bind with high affinity to this integrin. This study compares the influence of 99mTc-labeling applying novel Technetium-cores on imaging characteristics of the radiolabeled peptide.
Methods. Different peptide conjugates based on the cyclic pentapeptide c(RGDyK) (cRGD) were prepared and characterized (HYNIC-, Cys-, L2- and Pz1-cRGD). Radiolabeling experiments using different coligands for HYNIC-cRGD, the 99mTc(CO)3 metal fragment for PZ-1-cRGD (pyrazolyl-derivative), the Tc-nitrido-core using a phosphine-coligand (PNP) for Cys-cRGD and an isonitrile-conjugate (L2-cRGD) together with a NS3-coligand (4+1 concept) were performed and showed labeling yields >90% at high specific activities.
Results. A high in vitro stability was observed, plasma protein binding and lipophilicity varied considerably between different radiolabeled cRGD conjugates. Experiments on biological activity of the radiolabeled peptides using αvβ3 positive (M21) and negative (M21L) tumor cells did show specific uptake of various conjugates. Studies in tumor bearing animals revealed significant differences between different conjugates concerning pharmacokinetic behavior (predominant renal excretion to considerable hepatobiliary clearance) as well as tumor uptake (0.2-2.7%ID/g). Highest specific tumor uptake and tumor/background values were found for [99mTc]EDDA/HYNIC-c(RGDyK), [99mTc]Nitrido-PNP-Cys-c(RGDyK) and [99mTc(CO)3]-Pz1-c(RGDyK).
Conclusion. Using novel Tc-cores such as the 99mTc(CO)3 metal fragment, Tc-nitrido- and the 4+1 concept peptides could be labeled with [99mTc]technetium at high specific activities resulting in complexes with high stability, but binding moieties have to be optimized especially concerning hydrophilicity resulting in renal rather than hepatobiliary excretion. This comparative study underlines that peptide labeling strategies using 99mTc have to be properly selected and optimized. Different in vitro assays are necessary to predict targeting properties in vivo.

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