Clifford Thomas, Boswell C Andrew, Biddlecombe Grainne B, Lewis Jason S, Brechbiel Martin W
Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, Building 10 Center Drive, Bethesda, Maryland 20892-1088, USA.
J Med Chem. 2006 Jul 13;49(14):4297-304. doi: 10.1021/jm060317v.
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.
已开发出一种基于二乙三胺五乙酸（DTPA）预组织环己基衍生物（CHX-A''）的多功能双功能螯合剂，用于方便地用铋（III）、铟（III）、镥（III）或钇（III）的金属离子放射性核素对肽进行N端标记。这是通过合成具有戊二酸间隔基的CHX-A''（反式环己基二乙三胺五乙酸）的单-N-羟基琥珀酰亚胺基五叔丁酯衍生物来实现的。在溶液相中用该试剂对市售获得的奥曲肽的N端进行修饰，并展示了其随后用（111）铟（半衰期 = 2.8天）和（86）钇（半衰期 = 14.7小时）进行放射性标记的过程。给出了（86）钇-CHX-A''-奥曲肽在生长抑素受体阳性荷瘤大鼠模型中的小动物PET/CT成像结果，以验证该新型药物。
