99mTc-EDDA-Tricine-HYNIC-TOC versus 99mTc-EDDA-Tricine-HYNIC-TATE: Synthesis and Preclinical Result of Two NewRadiopharmaceuticals for Somatostatin Receptor Scintigraphy

摘要

Somatostatin receptor (SSTR) scintigraphy with indium-111 DTPA-Octreotide hasrnbecome a routine diagnostic procedure in oncology. However, it suffers from somerndrawbacks concerning the limited availability, suboptimal imaging properties and elevatedrnradiation burden of 111In. In this study the preclinical evaluation of two somatostatinrnanalogues Tyr3-Octreotide and Tyr3-octreotate labeled with technetium-99m usingrnbifunctional chelators (BFCs) based on the hydrazinonicotinamide (HYNIC) system inrncomparison with each other is described. Conjugates of both peptides with HYNIC werernprepared and radiolabeling performed at high specific activity using EDDA/tricine as coligandsrnfor HYNIC conjugates. In receptor binding study Tyr3-octreotate showed higherrnaffinity to sstr2 (IC50 = 1.1±0.2) than that Tyr3-octreotide (IC50 = 1.3±0.3), while for sstr3rn(IC50 = > 1000) and sstr5 (IC50 = 80±10) Tyr3-octreotate had lower affinity than Tyr3-rnoctreotide (IC50 = 128±22) and (IC50 = 50±12). 99mTc-EDDA-tricine-HYNIC-TATE showedrna specific and high rate of internalization into AR4-2J rat pancreatic tumor cells, which after 4rnh, was about one and half time higher than that of 99mTc-EDDA-tricine-HYNIC-TOC.rnBiodistribution studies in AR4-2J tumor-bearing rats showed rapid clearance from all sstrnegativerntissues except the kidneys for both analogues. At 4 h the uptake of 99mTc-EDDAtricine-rnHYNIC-TATE in kidneys and liver was lower than for 99mTc-EDDA-tricine-HYNICTOC,rnbut in the tumor and sstr-positive tissues, especially pancreas was more than 99mTc-rnEDDA-tricine-HYNIC-TOC. Clinical comparison of these two peptide-basedrnradiopharmaceutical are under way.