Preclinical evaluation of [99mTc/EDDA/tricine/HYNIC0, 1-Nal3, Thr8]-octreotide as a new analogue in the detection of somatostatin-receptor-positive tumors.
OBJECTIVE
Radiolabeled 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 labeling with (99m)Tc: [6-hydrazinopyridine-3-carboxylic acid (HYNIC(0)), 1-Nal(3), Thr(8)]-octreotide ([HYNIC]-NATE), using ethylenediamine-N,N'-diacetic acid (EDDA) and tricine as coligands.


METHODS
Synthesis was preformed on a solid phase using a standard Fmoc strategy. Labeling with (99m)Tc was performed at 100 degrees C for 10 min using SnCl(2) 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 sstr(2)-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 sstr(2). 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).


CONCLUSIONS
These data show that [(99m)Tc/EDDA/tricine/HYNIC]-NATE is a specific radioligand for the somatostatin-receptor-positive tumors and is a suitable candidate for clinical studies.
Gandomkar
Mostafa
M
Nuclear Science Research School, Nuclear Science & Technology Research Institute, Atomic Energy Organization of Iran, Tehran, Iran. msgandomkar@yahoo.com
Najafi
Reza
R
Shafiei
Mohammad
M
Mazidi
Mohammad
M
Ebrahimi
Sayed Esmaeil Sadat
SE
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D007202:Indicators and Reagents; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000378:metabolism; D015282:Octreotide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D011786:Quality Control; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D011917:Rats, Inbred Lew; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014018:Tissue Distribution
C524177:(technetium 99m-EDDA-tricine-HYNIC(0)-Nal(1)-Thr(8))octreotide; D007202:Indicators and Reagents; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; C492049:Sstr2 protein, mouse; D013004:Somatostatin; D015282:Octreotide