Abstract
111In l led on DTPA-DPhe1-octreotide has been applied currently in clinical imaging for tumors with somatostatin. However, 111In is cyclotron produced. The radiol led octreotide by 111In is expensive and not conveniently available. Since 99mTc is characteristic of excellent radionuclide with high-resolution 140.5k eV γ, a half-life 6h, economically and conveniently available from 99Mo-99mTc generator and extensively used in nuclear medicine. It will be significant to develop 99mTc l led octreotide instead of the 111In l led octreotide for clinical. In this study, we have attempted to label octreotide by 99mTc using [99mTc(CO)3(H2O)3]+ as the precursor. [99mTc(CO)3(H2O)3]+ was found to be readily prepared in aqueous sodium. 99mTc labeling by means of [99mTc(CO)3(H2O)3]+ as a precursor has become a novel approach on 99mTc chemistry and nuclear medicine. DPhe1-octreotide was labeled with [99mTc(CO)3(H2O)3]+ via as the hydrazinonicotinamide bifunctional chelating agent. [99mTc(CO)3(OH2) 3]+ and the conjugate of DPhe1-octreotide coupled with HYNIC were prepared respectively according to the previous reports [Alberto et al. J Am Chem Soc 120(1998) 7987 and Clemens Decristoforo et al. Nucl Med &Biology 26(1999)389]. For the labeling, [99mTc(CO)3(OH2) 3]+ and HYNIC-DPhe1- octreotide was mixed to react under pH 7 solution, at 75?C for 30 min. The labeling efficiency could reach to 90%. Characterization of [99mTc(CO)3(OH2) 3]+ and 99mTc(I) labeled HYNIC-DPhe1-octreotide were carried out by thin layer chromatography, and electrophoresis. The radio chemical purities for [99mTc(CO)3(OH2)3]+ and 99mTc(I)-HYNIC-DPhe1-octreotide were 90% and 90%, respectively. [99mTc(CO)3(OH2)3]+ was positive charged whereas 99mTc(I)-HYNIC- DPhe1-octreotide was negative charged according to electrophoresis results.It was evidenced by binding assay that HYNIC-DPhe1-octreotide retains its biological activity to bind SSTR. It was testified by animal model imaging that 99mTc(I)-HYNIC-DPhe1-octreotide could be uptaken by the rat tumor implanted with AR42J cell line, showing a clear imaging. The result has demonstrated that 99mTc(I)-HYNIC-DPhe1-octreotide has potential for imaging of tumors with SSTR .