Radiolabeling of HER2 specific Affibody(R) molecule with F-18.
Radiolabeling of HER2 specific Affibody(R) molecule with F-18.
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DOI：
10.1016/j.jfluchem.2008.06.021
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发表时间：
2008-09
影响因子：
1.9
通讯作者：
Capala, Jacek
中科院分区：
文献类型：
--
作者：
Kiesewetter, Dale O.;Kramer-Marek, Gabriela;Ma, Ying;Capala, Jacek
20-30% 的人类乳腺癌中存在人类表皮生长因子 2 (HER2)，这是疾病进展更快的预后指标，也是抗 HER2 单克隆抗体的治疗指标。由于文献证明同一患者的原发性肿瘤和转移性肿瘤之间的 HER2 标记物表达存在一些不一致，因此我们着手开发一种显像剂，可用于评估个体患者体内标记物浓度。制药公司 Affibody AB 优化了 Affibody 分子对 HER2 的特异性。两个 Affibody 分子（一个 7 kD 和一个 8 kD 蛋白质）被设计为具有单个羧基末端半胱氨酸，以便为各种类型的成像标记提供特定位置。我们利用[18F]氟苯甲酸和氨乙基马来酰亚胺之间的偶联反应制备了N-[2-(4-[18F]氟苯甲酰胺基)乙基]马来酰亚胺。然后，我们通过在含有 0.1% 抗坏血酸钠的磷酸盐缓冲盐水中在 pH 7.4 下孵育来优化这种放射性标记的马来酰亚胺与半胱氨酸的游离巯基的缀合。在 2 小时的合成中，从[ 18 F]氟化物中获得的放射性标记 Affibody 分子的总未校正产率约为 10%。这些缀合的 Affibody 分子的比活性为 2.51 ± 0.92 MBq/μg。通过 HPLC-MS 对产物进行的表征支持 [18F]FBEM 与 Affibody 分子的缀合。表达 HER2 的异种移植物的成功成像证明，放射性标记的 Affibody 分子保留了其结合特异性。
The presence of human epidermal growth factor type 2 (HER2) on 20–30% of human breast cancer is a prognostic indicator of more rapid disease progression and a therapeutic indicator for anti-HER2 monoclonal antibodies. Because the literature has demonstrated some discordance between primary and metastatic tumors in the same patient for expression of the HER2 marker, we set out to develop an imaging agent that could be used to assess the marker concentration in vivo in an individual patient. The pharmaceutical company Affibody AB has optimized the specificity of Affibody molecules for HER2. Two Affibody molecules, a 7 kD and an 8 kD protein, were designed with a single carboxy terminal cysteine in order to provide a specific location for the purposes of labeling for various types of imaging. We have prepared N-[2-(4-[18F]fluorobenzamido)ethyl]maleimide utilizing a coupling reaction between [18F]fluorobenzoic acid and aminoethylmaleimide. We then optimized the conjugation of this radiolabeled maleimide to the free sulfhydryl of cysteine by incubating at pH 7.4 in phosphate buffered saline containing 0.1% sodium ascorbate. An overall uncorrected yield of radiolabeled Affibody molecule of approximately 10% from [18F]fluoride was achieved in a 2 h synthesis. These conjugated Affibody molecules were obtained with a specific activity of 2.51 ± 0.92 MBq/µg. Characterization of the product by HPLC-MS supported the conjugation of [18F]FBEM with the Affibody molecule. The radiolabeled Affibody molecule retained its binding specificity as demonstrated by successful imaging of xenografts expressing HER2.
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影响因子：
3.1
作者：
Kiesewetter, DO;Jagoda, EM;Eckelman, WC
通讯作者：
Eckelman, WC
影响因子：
46.9
作者：
Smith-Jones, PM;Solit, DB;Larson, SM
通讯作者：
Larson, SM
影响因子：
7.3
作者：
Lang, LX;Jagoda, E;Eckelman, WC
通讯作者：
Eckelman, WC
影响因子：
2.9
作者：
Shafer, DE;Inman, JK;Lees, A
通讯作者：
Lees, A
影响因子：
4.7
作者：
Tran, Thuy;Engfeldt, Torun;Karlstroem, Amelie Eriksson
通讯作者：
Karlstroem, Amelie Eriksson