Design and evaluation of new Tc-99m-labeled lactam bridge-cyclized alpha-MSH peptides for melanoma imaging.
Design and evaluation of new Tc-99m-labeled lactam bridge-cyclized alpha-MSH peptides for melanoma imaging.
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DOI：
10.1021/mp3006984
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发表时间：
2013-04-01
影响因子：
4.9
通讯作者：
Miao Y
中科院分区：
文献类型：
--
作者：
Guo H;Gallazzi F;Miao Y
本研究的目的是研究新的99 mTc标记的内酰胺桥环化α-黑素细胞刺激激素（α-MSH）肽使用双功能螯合剂的黑色素瘤靶向和成像特性。合成MAG 3-GGNle-CycMSHhex、AcCG 3-GGNle-CycMSHhex和HYNIC-GGNle-CycMSHhex肽，并在B16/F1黑素瘤细胞中测定它们的黑皮质素-1（MC 1）受体结合亲和力。在注射后2小时在携带B16/F1黑素瘤的C57小鼠中测定99 mTc-MAG 3-GGNle-CycMSHhex、99 mTc-AcCG 3-GGNle-CycMSHhex、99 mTc（CO）3-HYNIC-GGNle-CycMSHhex和99 mTc（EDDA）-HYNIC-GGNle-CycMSHex的生物分布，以选择先导肽用于进一步评价。进一步检查了99 mTc（EDDA）-HYNIC-GGNle-CycMSHhex的黑素瘤靶向和成像特性，因为其高黑素瘤摄取和快速尿清除。MAG 3-GGNle-CycMSHhex、AcCG 3-GGNle-CycMSHhex和HYNIC-GGNle-CycMSHhex在B16/F1黑色素瘤细胞中的IC 50值分别为1.0 ± 0.05、1.2 ± 0.19和0.6 ± 0.04 nM。在这四种99 mTc-肽中，99 mTc（EDDA）-HYNIC-GGNle-CycMSHhex在注射后2 h表现出最高的黑素瘤摄取（14.14 ± 4.90%ID/g）和最快的尿清除（91.26 ± 1.96%ID）。99 mTc（EDDA）-HYNIC-GGNle-CycMSHhex显示出高的肿瘤与正常器官摄取比率，除了肾脏。在注射后4和24小时，99 mTc（EDDA）-HYNIC-GGNle-CycMSHhex的肿瘤/肾摄取比为2.50和3.55。在注射后2小时，使用99 mTc（EDDA）-HYNIC-GGNle-CycMSHhex作为成像探针，通过SPECT/CT清楚地可视化黑色素瘤病变。总体而言，高黑素瘤摄取加上99 mTc（EDDA）-HYNIC-GGNle-CycMSHhex的快速尿清除突出了其在未来用于转移性黑素瘤检测的潜力。
The purpose of this study was to examine the melanoma targeting and imaging properties of new 99mTc-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone (α-MSH) peptides using bifunctional chelating agents. MAG3-GGNle-CycMSHhex, AcCG3-GGNle-CycMSHhex and HYNIC-GGNle-CycMSHhex peptides were synthesized and their melanocortin-1 (MC1) receptor binding affinities were determined in B16/F1 melanoma cells. The biodistribution of 99mTc-MAG3-GGNle-CycMSHhex, 99mTc-AcCG3-GGNle-CycMSHhex, 99mTc(CO)3-HYNIC-GGNle-CycMSHhex and 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex were determined in B16/F1 melanoma-bearing C57 mice at 2 h post-injection to select a lead peptide for further evaluation. The melanoma targeting and imaging properties of 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex were further examined because of its high melanoma uptake and fast urinary clearance. The IC50 values of MAG3-GGNle-CycMSHhex, AcCG3-GGNle-CycMSHhex and HYNIC-GGNle-CycMSHhex were 1.0 ± 0.05, 1.2 ± 0.19 and 0.6 ± 0.04 nM in B16/F1 melanoma cells, respectively. Among these four 99mTc-peptides, 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex exhibited the highest melanoma uptake (14.14 ± 4.90% ID/g) and fastest urinary clearance (91.26 ± 1.96% ID) at 2 h post-injection. 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex showed high tumor to normal organ uptake ratios except for the kidneys. The tumor/kidney uptake ratios of 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex were 2.50 and 3.55 at 4 and 24 h post-injection. The melanoma lesions were clearly visualized by SPECT/CT using 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex as an imaging probe at 2 h post-injection. Overall, high melanoma uptake coupled with fast urinary clearance of 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex highlighted its potential for metastatic melanoma detection in the future.
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影响因子：
3
作者：
Raposinho, Paula D.;Xavier, Catarina;Santos, Isabel
通讯作者：
Santos, Isabel
DOI：
10.2967/jnumed.110.086009
发表时间：
2011-04
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Guo H;Yang J;Gallazzi F;Miao Y
通讯作者：
Miao Y
DOI：
10.1073/pnas.95.22.12814
发表时间：
1998-10-27
影响因子：
11.1
作者：
Giblin, MF;Wang, N;Quinn, TP
通讯作者：
Quinn, TP
影响因子：
7.3
作者：
Cheng, Z;Chen, JQ;Jurisson, SS
通讯作者：
Jurisson, SS
影响因子：
3.1
作者：
Chen, JQ;Giblin, MF;Quinn, TP
通讯作者：
Quinn, TP