title: Validation of a novel CHX-A'' derivative suitable for peptide conjugation: small animal PET/CT imaging using yttrium-86-CHX-A''-octreotide.
abstract: A versatile bifunctional chelating reagent based on a preorganized cyclohexyl derivative of DTPA (CHX-A'') has been developed for the convenient N-terminal labeling of peptides with metal ion radionuclides of Bi(III), In(III), Lu(III), or Y(III). This was achieved via the synthesis of a mono-N-hydroxysuccinimidyl penta-tert-butyl ester derivative of CHX-A'' (trans-cyclohexyldiethylenetriaminepenta-acetic acid) featuring a glutaric acid spacer. Commercially obtained octreotide was modified at its N-terminus by this reagent in the solution phase, and its subsequent radiolabeling with (111)In (T(1/2) = 2.8 d) and (86)Y (T(1/2) = 14.7 h) demonstrated. Small animal PET/CT imaging results of (86)Y-CHX-A''-octreotide in a somatostatin receptor-positive tumor-bearing rat model are presented for the validation of the novel agent.
authors.affiliation: Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, Building 10 Center Drive, Bethesda, Maryland 20892-1088, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Clifford
authors.forename: C Andrew
authors.initials: CA
authors.lastname: Boswell
authors.forename: Grainne B
authors.initials: GB
authors.lastname: Biddlecombe
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lewis
authors.forename: Martin W
authors.initials: MW
authors.lastname: Brechbiel
mesh_terms: D000818:Animals; D017879:Isothiocyanates / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D007553:Isotope Labeling; D008297:Male; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging; D015282:Octreotide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D011917:Rats, Inbred Lew; D014018:Tissue Distribution; D015021:Yttrium Radioisotopes
chemical_list: D017879:Isothiocyanates; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; C513159:yttrium cyclohexyldiethylenetriaminepentaacetic acid-octreotide; C085678:N-(2-amino-3-(4-isothiocyanatophenyl)propyl)cyclohexane-1,2-diamine-N,N',N',N'',N''-pentaacetic acid; D004369:Pentetic Acid; D015282:Octreotide