PURPOSE: Despite excellent radionuclide characteristics, no (18)F-labeled peptides are available for quantitative peptide receptor mapping using positron emission tomography (PET) so far, mainly due to time-consuming multistep radiosyntheses with limited overall yields. A newly developed two-step chemoselective conjugation method allows rapid and high-yield [(18)F]fluorination of peptides via oxime formation and was applied for the synthesis of new (18)F-labeled carbohydrated Tyr(3)-octreotate (TOCA) analogs with optimized pharmacokinetics suitable for clinical routine somatostatin-receptor (sst) imaging. EXPERIMENTAL DESIGN: (18)F-labeled glucose (Gluc-S-) and cellobiose (Cel-S-) derivatives of aminooxy-functionalized TOCA were synthesized via oxime formation with 4-[(18)F]fluorobenzaldehyde ([(18)F]FBOA-peptides). Both the in vitro internalization profile of Gluc-S-Dpr([(18)F]FBOA)TOCA and Cel-S-Dpr([(18)F]FBOA)TOCA in hsst(2)-expressing Chinese hamster ovary cells (dual tracer protocol) and their biodistribution in AR42J tumor-bearing mice were investigated and compared with two [(18)F]fluoropropionylated ([(18)F]FP) analogs, Gluc-Lys([(18)F]FP)TOCA and Gluc-S-Dpr([(18)F]FP)TOCA. RESULTS: In contrast to [(18)F]FP-labeling (3 h), chemo-selective [(18)F]FBOA-formation (50 min) afforded the respective radiopeptides in high yields (65-85%). In vitro, Gluc-S-Dpr([(18)F]FBOA)TOCA and Cel-S-Dpr([(18)F]FBOA)-TOCA showed high internalization (139 +/- 2 and 163 +/- 8 of the reference [(125)I]Tyr(3)-octreotide, respectively), which was reflected by high tumor accumulation in vivo [21.8 +/- 1.4 and 24.0 +/- 2.5% of injected dose/g (1 h), respectively]. How-ever, only Cel-S-Dpr([(18)F]FBOA)TOCA and Gluc-S-Dpr([(18)F]FP)TOCA (tumor: 15.1 +/- 1.5% of injected dose/g) with its very low accumulation in all of the nontarget organs showed improved tumor:organ ratios compared with Gluc-Lys([(18)F]FP)TOCA. For Cel-S-Dpr([(18)F]FBOA)TOCA,tumor:organ ratios (1 h) were 42:1, 27:1, 15:1, 3:1, and 208:1 for blood, liver, intestine, kidney, and muscle, respectively. CONCLUSION: Due to the fast and high-yield chemoselective radiofluorination strategy and to its excellent pharmacokinetics, Cel-S-Dpr([(18)F]FBOA)TOCA represents the first tracer suitable for routine clinical application in PET somatostatin receptor imaging.     «

PURPOSE: Despite excellent radionuclide characteristics, no (18)F-labeled peptides are available for quantitative peptide receptor mapping using positron emission tomography (PET) so far, mainly due to time-consuming multistep radiosyntheses with limited overall yields. A newly developed two-step chemoselective conjugation method allows rapid and high-yield [(18)F]fluorination of peptides via oxime formation and was applied for the synthesis of new (18)F-labeled carbohydrated Tyr(3)-octreotate (...     »