Synthesis of octreotide-dextran-avidin for pretargeted peptide imaging and therapy of cancer

Objectives Pretargeted radioimmnoimaging and radioimmunotherapy of cancer using biotin and avidin system have achieved promising results. The aim of this study was to synthesis and evaluation of octreotide-dextran-avidin to explore and establish a possible method for pretargeted peptide imaging and therapy of cancer.

Methods Dextran was oxidized with sodium periodate and subsequently reacted with octreotide and avidin. The conjugate was then stabilized by reducing Schiff bases with sodium cyanoborohydirde. The concentration of avidin in final conjugate was determined by spectrophotometric method. The receptor binding affinity of octreotide-dextran-avidin was tested in vitro on rat brain cortex membranes by competition against octreotide. The octreotide-dextran-avidin conjugate was then tested for the affinity towards to biotin by the spectrophotometric method known as HABA assay based on the use of 4-hydroxazobenzene-2-carboxylic acid. The radioiodination of octreotide-dextran-avidin was carried out by Iodogen method. The biodistribution and blood clearance of radioiodinated octreotide-dextran-avidin were investigated in normal rats.

Results The high purity of octreotide-dextran-avidin conjugatewas achieved with 80% yield. The octreotide-dextran-avidin showed high somatostatin receptor binding affinity and also retained complete affinity for biotin. The biodistribution showed that the excretion of the conjugate was mainly through liver and kidneys. High uptake was seen in the adrenals and almost kept same during 24 h. In all other organs the radioactivity was more rapidly eliminated.

Conclusions The octreotide-dextran-avidin conjugate shows promising properties and is worthy of further investigation for pretargeted peptide imaging and therapy of cancer.

Research Support This work was supported by the National Natural Science Foundation of China (No.30670584).