title: 99mTc-labeled RGD-BBN peptide for small-animal SPECT/CT of lung carcinoma.
abstract: We recently designed and synthesized a Glu-c(RGDyK)-bombesin (RGD-BBN) heterodimeric peptide exhibiting a dual integrin α(v)β(3) and gastrin-releasing peptide receptor (GRPR) targeting property. In this study, we investigated whether (99m)Tc-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 (99m)Tc using tricine and TPPTS as the coligands (TPPTS = trisodium triphenylphosphine-3,3',3"-trisulfonate). The biodistribution, planar gamma imaging, and small-animal SPECT/CT studies of (99m)Tc-HYNIC(tricine)(TPPTS)-RGD-BBN ((99m)Tc-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 α(v)β(3) and GRPR binding capacity. (99m)Tc-RGD-BBN was prepared with a high radiochemical purity (>98%), and it exhibited specific tumor imaging with high contrast to the contralateral background. (99m)Tc-RGD-BBN was superior to (18)F-FDG for distinguishing lung carcinoma from inflammation. The uptake of (99m)Tc-RGD-BBN in LLC xenografts was 2.69 ± 0.66% ID/g at 1 h postinjection (p.i.) and was decreased to 1.99 ± 0.61% ID/g at 2 h p.i. The inflammation uptake of (99m)Tc-RGD-BBN was 1.20 ± 0.32% ID/g at 1 h and 0.56 ± 0.17% ID/g at 2 h p.i., respectively. High pancreas uptake (25.76 ± 5.49%ID/g and 19.56 ± 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 (99m)Tc-RGD-BBN can specifically detect the LLC pulmonary metastases. Our results suggested that SPECT/CT with (99m)Tc-RGD-BBN would provide an effective approach for the noninvasive detection of lung cancer.
authors.affiliation: Medical Isotopes Research Center, Peking University, Beijing 100191, China. liuzf@bjmu.edu.cn
authors.forename: Zhaofei
authors.initials: Z
authors.lastname: Liu
authors.forename: Jinming
authors.initials: J
authors.lastname: Huang
authors.forename: Chengyan
authors.initials: C
authors.lastname: Dong
authors.forename: Liyang
authors.initials: L
authors.lastname: Cui
authors.forename: Xiaona
authors.initials: X
authors.lastname: Jin
authors.forename: Bing
authors.initials: B
authors.lastname: Jia
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhu
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D001839:Bombesin / Q000737:chemistry*; D002277:Carcinoma / Q000175:diagnosis*; D018827:Carcinoma, Lewis Lung / Q000175:diagnosis; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000737:chemistry*; D015609:Organotechnetium Compounds / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000737:chemistry; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D009842:Oligopeptides; D015609:Organotechnetium Compounds; D010455:Peptides; D019275:Radiopharmaceuticals; C047981:arginyl-glycyl-aspartic acid; D001839:Bombesin