99m Tc-Labeling of HYNIC-Conjugated Cyclic RGDfK Dimer and Tetramer Using EDDA as Coligand
2008; American Chemical Society; Volume: 19; Issue: 3 Linguagem: Inglês
10.1021/bc7004208
ISSN1520-4812
AutoresJianjun Wang, Young‐Seung Kim, Shuang Liu,
Tópico(s)Medical Imaging Techniques and Applications
ResumoIn this study, EDDA (ethylenediamine-N,N′-diacetic acid) was used as the coligand for 99mTc-labeling of cyclic RGDfK conjugates: HYNIC−dimer (HYNIC = 6-hydrazinonicotinamide; dimer = E[c(RGDfK)]2) and HYNIC−tetramer (tetramer = E{E[c(RGDfK)]2}2). First, HYNIC−dimer was allowed to react with 99mTcO4− in the presence of excess tricine and stannous chloride to form the intermediate complex [99mTc(HYNIC−dimer)(tricine)2], which was then allowed to react with EDDA to afford [99mTc(HYNIC−dimer)(EDDA)] with high yield (>90%) and high specific activity (∼8.0 Ci/µmol). Under the same radiolabeling conditions, the yield for [99mTc(HYNIC−tetramer)(EDDA)] was always <65%. The results from a mixed-ligand experiment show that there is only one EDDA bonding to the 99mTc-HYNIC core in [99mTc(HYNIC−dimer)(EDDA)]. The athymic nude mice bearing subcutaneous U87MG human glioma xenografts were used to evaluate the impact of EDDA coligand on the biodistribution characteristics and excretion kinetics of the 99mTc-labeled HYNIC−dimer and HYNIC−tetramer. Surprisingly, [99mTc(HYNIC−dimer)(EDDA)] and [99mTc(HYNIC−tetramer)(EDDA)] had almost identical tumor uptake over the 2 h period. The use of EDDA as coligand to replace tricine/TPPTS (TPPTS = trisodium triphenylphosphine-3,3′,3′′-trisulfonate) did not significantly change the uptake of the 99mTc-labeled HYNIC-dimer in noncancerous organs, such as the liver, kidneys, and lungs; but it did result in a significantly lower kidney uptake for the 99mTc-labeled HYNIC−tetramer due to faster renal excretion. It was also found that the radiotracer tumor uptake decreases in a linear fashion as the tumor size increases. The smaller the tumors are, the higher the tumor uptake is regardless of the identity of radiotracer.
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