Radiola
beled somatostatin analogues are important tools for the in vivo localization and targeted radionuclide therapy of somatostatin-receptor-positive tumors. The aim of this study was to evaluate a new somatostatin analogue designed for the la
beling with
99mTc: [6-hydrazinopyridine-3-car
boxylic acid (HYNIC
0), 1-Nal
3, Thr
8]-octreotide ([HYNIC]-NATE), using ethylenediamine-
N,
N′-diacetic acid (EDDA) and t
ricine as coligands.
Methods
Synthesis was preformed on a solid phase using a standard Fmoc strategy. Labeling with 99mTc was performed at 100°C for 10 min using SnClb>2b> as a reductant. Radiochemical analysis involved ITLC and high-performance liquid chromatography methods. Peptide conjugate affinity was determined in AR4-2J cell membranes. The internalization and externalization rates were studied in sstrb>2b>-expressing AR4-2J cells. Biodistribution of radiopeptide was studied in rats bearing the AR4-2J tumor.
Results
Radiolabeling was performed at high specific activities, and radiochemical purity was >95%. Peptide conjugate showed high affinity binding for sstrb>2b>. The radioligand showed a moderate and specific internalization into AR4-2J cells (14.13±0.61%at 4 h). In animal biodistribution studies, a receptor-specific uptake of radioactivity was observed in somatostatin-receptor-positive organs. After 4 h, uptake in the AR4-2J tumor was 1.33±0.23%ID/g (percentage of injected dose per gram of tissue).
Conclusion
These data show that [99mTc/EDDA/tricine/HYNIC]-NATE is a specific radioligand for the somatostatin-receptor-positive tumors and is a suitable candidate for clinical studies.
