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Response to Comment on “In Vitro and in Vivo Evaluation of a Technetium-99m-Labeled Cyclic RGD Peptide as a Specific Marker of rVβ3 Integrin for Tumor Imaging” Sir: The report in question (1) describes an investigation into the properties of 99mTc-RGD-4C for tumor imaging. As is evident therein, our results were disappointing in that unsatisfactory tumor targeting was observed in two xenografts (LS174T and ACHN) in nude mice. In the conclusion of that report, we state that other investigators imaging the same receptor with cyclic RGD peptides have also experienced “marginal” results and, as an example, we cited the work of Dr. Haubner et al. (2). In retrospect, it was somewhat unfair to do so since the peptides are quite different. Whereas the RGD-4C used in our investigation was cyclized via two disulfide bridges, the RGD of Haubner et al. was cyclized via an amide bond. While Haubner et al. labeled with radioiodine via an attached tyrosine, we radiolabeled with 99m Tc via hynic/tricine. Furthermore, the RGD of Haubner et al. was glycosylated to improve pharmacokinetics. Finally, the tumor models used by Haubner et al. are reported to show a high expression of the receptor whereas the receptor concentration of the LS174T and ACHN tumors are unknown and were not measured by us. Under these conditions, the tumor uptake reported by Haubner et al. was decidedly superior at about 3%ID/g and could be inhibited vs about 0.7% ID/g in our case with no difference from control. But whether both studies are “marginal” is best left to the readership to decide. In the final sentence of our abstract, we conclude that “RGD peptides may have limitations as tumor imaging
agents” because of low receptor numbers or low binding affinities. We recognize that binding affinities considerably higher than the micromolar value of our radiolabeled RGD-4C have been reported for other RGD peptides. Whether due to higher affinities or higher receptor numbers, we would be delighted to be proven wrong. LITERATURE CITED (1) Su, Z. F., Liu, G., Gupta, S., Zhu, Z., Rusckowski, M., and Hnatowich, D. J. In Vitro and in Vivo Evaluation of a Technetium-99m-Labeled Cyclic RGD Peptide as a Specific Marker of RVβ3 Integrin for Tumor Imaging. Bioconjugate Chem. 13, 561570. (2) Haubner, R., Wester, H. J., Burkhart, F., SenekowitschSchmidtke, R., Weber, W., Goodman, S. L., et al. (2001) Glycosylated RGD-containing peptides: tracer for tumor targeting and angiogenesis imaging with improved biokinetics. J. Nucl. Med. 42, 326-336.
Donald Hnatowich University of Massachusetts Medical Center Nuclear Medicine Department 55 Lake Avenue North Worcester, Massachusetts 01655 E-mail:
[email protected] BC020085O
10.1021/bc020085o CCC: $25.00 © 2003 American Chemical Society Published on Web 02/28/2003
