[18F]Galacto-RGD: Synthesis, Radiolabeling, Metabolic Stability, and Radiation Dose Estimates

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• 作者：Roland Haubner ; Bertrand Kuhnast ; Christian Mang ; Wolfgang A. Weber ; Horst Kessler ; Hans-Jü ; rgen Wester ; and Markus Schwaiger
• 刊名：Bioconjugate Chemistry
• 出版年：2004
• 出版时间：January 2004
• 年：2004
• 卷：15
• 期：1
• 页码：61 - 69
• 全文大小：188K
• 年卷期：v.15,no.1(January 2004)
• ISSN：1520-4812

文摘

It has been demonstrated in various murine tumor models that radiolabeled RGD-peptides can beused for noninvasive determination of rs/alpha.gif" BORDER=0>vrs/beta2.gif" BORDER=0 ALIGN="middle">3 integrin expression. Introduction of sugar moietiesimproved the pharmacokinetic properties of these peptides and led to tracer with good tumor-to-background ratios. Here we describe the synthesis, radiolabeling, and the metabolic stability of aglycosylated RGD-peptide ([¹⁸F]Galacto-RGD) and give first radiation dose estimates for this tracer.The peptide was assembled on a solid support using Fmoc-protocols and cyclized under high dilutionconditions. It was conjugated with a sugar amino acid, which can be synthesized via a four-stepsynthesis starting from pentaacetyl-protected galactose. For radiolabeling of the glycopeptide,4-nitrophenyl-2-[¹⁸F]fluoropropionate was used. This prosthetic group allowed synthesis of [¹⁸F]Galacto-RGD with a maximum decay-corrected radiochemical yield of up to 85% and radiochemical purity>98%. The overall radiochemical yield was 29 ± 5% with a total reaction time including final HPLCpreparation of 200 ± 18 min. The metabolic stability of [¹⁸F]Galacto-RGD was determined in mouseblood and liver, kidney, and tumor homogenates 2 h after tracer injection. The average fraction ofintact tracer in these organs was approximately 87%, 76%, 69%, and 87%, respectively, indicatinghigh in vivo stability of the radiolabeled glycopeptide. The expected radiation dose to humans afterinjection of [¹⁸F]Galacto-RGD has been estimated on the basis of dynamic PET studies with NewZealand white rabbits. According to the residence times in these animals the effective dose wascalculated using the MIRDOSE 3.0 program as 2.2 × 10^-2 mGy/MBq. In conclusion, [¹⁸F]Galacto-RGD can be synthesized in high radiochemical yields and radiochemical purity. Despite the time-consuming synthesis of the prosthetic group 185 MBq of [¹⁸F]Galacto-RGD, a sufficient dose for patientstudies, can be produced starting with approximately 2.2 GBq of [¹⁸F]flouride. Moreover, the fastexcretion, the suitable metabolic stability and the low estimated radiation dose allow to evaluate thistracer in human studies.