A HER2-binding Affibody molecule labelled with 68Ga for PET imaging: direct in vivo comparison with the 111In-labelled analogue

被引:76
作者
Tolmachev, Vladimir [1 ,2 ]
Velikyan, Irina [3 ,4 ]
Sandstrom, Mattias [5 ]
Orlova, Anna [1 ]
机构
[1] Uppsala Univ, Div Biomed Radiat Sci, Rudbeck Lab, S-75181 Uppsala, Sweden
[2] Uppsala Univ, Div Nucl Med, Dept Med Sci, S-75181 Uppsala, Sweden
[3] Uppsala Univ, Dept Biochem & Organ Chem, S-75181 Uppsala, Sweden
[4] GE Healthcare, GEMS PET Syst, Uppsala Appl Sci Lab, Uppsala, Sweden
[5] Univ Uppsala Hosp, Dept Oncol, Hosp Phys, S-75185 Uppsala, Sweden
基金
瑞典研究理事会;
关键词
Affibody molecule; HER2; Ga-68; Tumour targeting; Molecular imaging; HER-2/NEU EXPRESSION; SOMATOSTATIN ANALOG; HER2; EXPRESSION; PROSTATE-CANCER; BREAST-CANCER; OVEREXPRESSION; PEPTIDES; THERAPY; BIODISTRIBUTION; ONCOPROTEIN;
D O I
10.1007/s00259-009-1367-7
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
Overexpression of HER2 receptors is a prognostic and predictive biomarker in breast cancer and a number of other malignancies. Radionuclide molecular imaging of HER2 overexpression may influence patient management making treatment more personalized. Earlier, In-111-DOTA-Z(HER2:342-pep2) (ABY-002) Affibody molecule demonstrated excellent imaging of HER2-expressing xenografts in mice shortly after injection. The use of the positron-emitting nuclide Ga-68 instead of In-111 might increase both the sensitivity of HER2 imaging and accuracy of expression quantification. The goal of this study was to prepare and characterize Ga-68-labelled ABY-002. Ga-68 labelling of ABY-002 was optimized. In vitro cell binding and procession of Ga-68-ABY-002 was evaluated. Biodistribution and tumour targeting of Ga-68-ABY-002 and In-111-ABY-002 was compared in vivo by paired-label experiments. ABY-002 was incubated with Ga-68 at 90A degrees C for 10 min resulting in a radiochemical labelling yield of over 95%. Capacity for specific binding to HER2-expressing cells was retained. In vivo, both Ga-68-ABY-002 and In-111-ABY-002 demonstrated specific targeting of SKOV-3 xenografts and high-contrast imaging. Background radioactivity in blood, lungs, gastrointestinal tract and muscle fell more rapidly for Ga-68-ABY-002 compared with In-111-ABY-002 favouring imaging shortly after injection. For Ga-68-ABY-002, a tumour uptake of 12.4 A +/- 3.8%ID/g and a tumour to blood ratio of 31 A +/- 13 were achieved at 2 h post-injection. Ga-68-ABY-002 is easy to label and provides high-contrast imaging within 2 h after injection. This makes it a promising candidate for clinical molecular imaging of HER2 expression in malignant tumours.
引用
收藏
页码:1356 / 1367
页数:12
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