99mTc-Labeled RGD-BBN Peptide for Small-Animal SPECT/CT of Lung Carcinoma

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• 作者：Zhaofei Liu ; Jinming Huang ; Chengyan Dong ; Liyang Cui ; Xiaona Jin ; Bing Jia ; Zhaohui Zhu ; Fang Li ; Fan Wang
• 刊名：Molecular Pharmaceutics
• 出版年：2012
• 出版时间：May 7, 2012
• 年：2012
• 卷：9
• 期：5
• 页码：1409-1417
• 全文大小：456K
• 年卷期：v.9,no.5(May 7, 2012)
• ISSN：1543-8392

文摘

We recently designed and synthesized a Glu-c(RGDyK)-bombesin (RGD-BBN) heterodimeric peptide exhibiting a dual integrin 伪_v尾₃ and gastrin-releasing peptide receptor (GRPR) targeting property. In this study, we investigated whether ^99mTc-labeled RGD-BBN peptide could be used for the noninvasive detection of lung carcinoma by using small-animal single-photon emission computed tomography (SPECT)/CT. RGD-BBN peptide was conjugated with 6-hydrazinonicotinyl (HYNIC) and then radiolabeled with ^99mTc using tricine and TPPTS as the coligands (TPPTS = trisodium triphenylphosphine-3,3鈥?3鈥?trisulfonate). The biodistribution, planar gamma imaging, and small-animal SPECT/CT studies of ^99mTc-HYNIC(tricine)(TPPTS)-RGD-BBN (^99mTc-RGD-BBN) were performed in C57/BL6 mice bearing Lewis lung carcinoma (LLC) or bearing both inflammation and LLC. HYNIC-RGD-BBN possessed a dual integrin 伪_v尾₃ and GRPR binding capacity. ^99mTc-RGD-BBN was prepared with a high radiochemical purity (>98%), and it exhibited specific tumor imaging with high contrast to the contralateral background. ^99mTc-RGD-BBN was superior to ¹⁸F-FDG for distinguishing lung carcinoma from inflammation. The uptake of ^99mTc-RGD-BBN in LLC xenografts was 2.69 卤 0.66% ID/g at 1 h postinjection (p.i.) and was decreased to 1.99 卤 0.61% ID/g at 2 h p.i. The inflammation uptake of ^99mTc-RGD-BBN was 1.20 卤 0.32% ID/g at 1 h and 0.56 卤 0.17% ID/g at 2 h p.i., respectively. High pancreas uptake (25.76 卤 5.49%ID/g and 19.56 卤 6.78% ID/g at 1 and 2 h p.i., respectively) was also found due to the high GRPR expression of this organ. Small-animal SPECT/CT using ^99mTc-RGD-BBN can specifically detect the LLC pulmonary metastases. Our results suggested that SPECT/CT with ^99mTc-RGD-BBN would provide an effective approach for the noninvasive detection of lung cancer.

Keywords:

RGD-bombesin; integrin 伪_v尾₃; GRPR; lung carcinoma; single-photon emission computed tomography (SPECT)