DARU Journal of Pharmaceutical Sciences 2006. 14(4):183-190.

Synthesis, development and preclinical comparison of two new peptide based freeze-dried kit formulation 99mTc-EDDA-Tricine-HYNIC-TOC and 99mTc-EDDA-Tricine-HYNIC-TATE for somatostatin receptor positive tumor scintigraphy
Gandomkar M., Najafi R., Babaei M.H., Shafiei M., Sadat Ebrahimi S. E.


Somatostatin receptor (sstr) scintigraphy with [111In diethylenetriaminepentaacetic acid]-octreotide ([111In-DTPA]-OC) has became a routine diagnostic procedure in oncology. However, it suffers from some drawbacks concerning the limited availability, suboptimal imaging properties and elevated radiation burden of 111In.
In this study synthesis, conjugation and preclinical evaluation of two new freeze-dried kit formulation based on somatostatin analogues, Tyr3-Octreotide (TOC) and Tyr3-octreotate (TATE), designed for the labeling with 99mTc are described.
After cleavage from the resin and preparation of the cyclized peptides, these compounds were conjugated with 6-hydrazinopyridine-3-carboxylic acid (HYNIC) in solution. Radiolabeling of HYNIC peptide conjugates was performed at high specific activity using one-step kits formulation based on tricine and ethylenediamine-N,N′ -diacetic acid (EDDA) as co-ligands.
Both, 6-hydrazinopyridine-3-carboxylic acid0-Tyr3-Octreotide (HYNIC-TOC) and 6-hydrazinopyridine-3-carboxylic acid0-Tyr3-Octreotate (HYNIC-TATE), showed a specific and high rate of internalization after 4 h in AR4-2J rat pancreatic tumor cells, (11.2±0.8 and 18.1±1.2 respectively).
Biodistribution studies in AR4-2J tumor-bearing rats showed rapid clearance of both analogues from all sstr-negative tissues except the kidneys. The specific uptake in tumor and sstr-positive tissues especially pituitary, pancreas and adrenals were observed. After 4 h the adrenals to pancreas uptake ratio for HYNIC-TOC was higher than that of HYNIC-TATE. Although both compounds had high kidney and low liver excretion, for HYNIC-TATE, it was lower. The results suggest these two new peptide based freeze-dried kits might be of great promise for clinical application in imaging of somatostatin receptor-positive tumors.


Kit formulation,

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