Preparation, 99mTc-labeling, and in vitro characterization of HYNIC and N3S modified RC-160 and [Tyr3]octreotide
Preparation, 99mTc-labeling, and in vitro characterization of HYNIC and N3S modified RC-160 and [Tyr3]octreotide
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DOI：
10.1021/bc980121c
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发表时间：
1999-05-01
影响因子：
4.7
通讯作者：
Mather, SJ
中科院分区：
文献类型：
--
作者：
Decristoforo, C;Mather, SJ
本文报道了两种生长抑素类似物RC-160和[Tyr(3)]octretic与不同双功能螯合剂的偶联物的合成，用于~(99)T标记。小规模、高纯度地制备了与烟酰肼(HYNIC)和两个N3S化合物(苯甲酰MAG3和N3S己二酸酯衍生物)的偶联物，使不同的双功能螯合剂可以在同一多肽上进行评价，而不需要进行广泛的多肽合成。除N3S己二酸酯外，所有结合物均具有较高的体外稳定性和结合亲和力。用~(99)m标记的多肽结合物具有较高的比活度(~gt；1Ci/mU·m o l)，并探索了不同配体的HYNIC结合物。由此得到的放射性标记络合物高度稳定，并显示出与纳摩尔范围内的生长抑素受体的结合亲和力。不同配体标记HYNIC结合物的产率、稳定性、亲脂性和异构性不同，与Tricine相比，EDDA和Tricine/Nicotinic的配位异构体较少，亲脂性较低，稳定性较高。特别是，HYNIC络合物在进一步的体内评估中显示了良好的结果。
The synthesis of conjugates of two somatostatin analogues, RC-160 and [Tyr(3)]octreotide with different bifunctional chelators for labeling with Tc-99m, is described. Conjugates with hydrazinonicotinamide (HYNIC) and two N3S compounds (benzoyl MAG3 and a N3S adipate derivative) were prepared on a small scale with high purity allowing evaluation of different bifunctional chelators on the same peptide without extensive peptide synthesis. High in vitro stability and retained binding affinity was found for all conjugates except for the N3S adipate. Peptide conjugates could be labeled at high specific activities (>1 Ci/mu mol) with Tc-99m, and different coligands were explored for the HYNIC conjugates. The resulting radiolabeled complexes were highly stable and showed binding affinity to somatostatin receptors in the nanomolar range. Varying labeling yield, stability, lipophilicity, and isomerism were found for different coligands used for labeling HYNIC conjugates, with lower lipophilicity, higher stability, and fewer coordination isomers for EDDA and tricine/nicotinic acid as ternary coligand compared to tricine. In particular, HYNIC complexes showed promising results for further in vivo evaluation.