99MTC-EDDA/HYNIC-TOC AND 99MTC-EDDA/HYNIC-TATE –THREE YEARSEXPERIENCE

摘要

Somatostatin is a naturally occurring 14-amino acid peptide which controls the secretion ofrnmany hormones [1]. A high dentisity of somatostatin receptors have been found on tumors mainly ofrnneuroendocrine origin. Somatostatin has a very short biological half-life of several minutes, hamperingrnsufficient receptor binding to allow adequate imaging. Derivatives of somatostatin represent the mostrnimportant peptides for receptor targeting in oncological applications. In this study two promisingrnradiopharmaceuticals 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE with the potential to replace 111In-rnDTPA-D-Phe1-Octreotide in somatostatin receptor scintigraphy are presented [2]. HYNIC – Tyr3-rnoctreotide (HYNIC – TOC) and HYNIC – Tyr3 – Octreotate (HYNIC - TATE) were synthesized inrnour laboratory on solid phase using the Fmoc strategy. The overall yields were between 14% and 20rn%. Wet 99mTc-labelling of HYNIC-TOC and HYNIC-TATE were performed to optimize the amountrnand concentration of reagents, temperature and reaction time which was then transferred to HYNICTOCrnand HYNIC-TATE dry kit formulation. The kit consist of two vials: the first vial: 20 μg HYNICTOCrnor HYNIC-TATE, 40 μg SnCl2, 50 mg tricine, 10 mg mannitol, the second vial: 10 mgrnEDDA(ethylenediamine-N,N'-diacetic acid). Radiolabelling was carried out by the addition about 1 mlrnof generator eluate (20-40mCi radioactivity) to the vial with HYNIC-TOC or HYNIC-TATE whichrnwas prepared by adding 0.5 ml EDDA. The mixture was incubated by 20 min at 80oC. Radiochemicalrnpurity of 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE, controlled by TLC and HPLC methodsrnshowed over 90% radiochemical yield and percentage of unbound free 99mTc-pertechnetate as well asrncolloidal forms of 99mTc was in the range of 2 - 3%. The radiochemical purity of the freeze-dried kitsrnduring storage at 2-8oC was checked once a month by radiolabelling and determination of thernradiochemical purity by HPLC. The stability of these kits was determined for 1 year. Stability of thernobtained kits allowed extensive clinical studies of 99mTc-HYNIC-Tyr3-octreotide and 99mTc-HYNICTyr3-rnOctreotate.