Preparation of F-18 labeled annexin V:: a potential PET radiopharmaceutical for imaging cell death
Preparation of F-18 labeled annexin V:: a potential PET radiopharmaceutical for imaging cell death
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DOI：
10.1016/j.nucmedbio.2004.02.007
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发表时间：
2004-08-01
影响因子：
3.1
通讯作者：
Mease, RC
中科院分区：
文献类型：
--
作者：
Toretsky, J;Levenson, A;Mease, RC
对抗肿瘤治疗的临床反应是在化疗后6-12周使用影像学（如CT或MRI）来测量的。当时的图像既反映了肿瘤细胞的死亡，也反映了新的生长。因此，化疗引起的肿瘤细胞死亡的数量不能用目前的成像方式有效地量化。需要在化疗后立即对肿瘤细胞死亡进行定量测量，以帮助验证新药物并优化现有疗法的管理。膜联蛋白V是一种36kD的蛋白，与濒死细胞上暴露的磷脂酰丝氨酸（PS）结合。为了合成一种能在体内检测细胞死亡的探针，我们将正电子发射器F-18通过化合物N-琥珀酰酰-4-[F-18]氟苯甲酸盐[F-18]SFB偶联到膜联蛋白V上。在3小时内，F-18氟化物中F-18标记的膜联蛋白V的衰变校正放射化学产率为17.6+/- 5.6% （n=4）。当蛋白浓度为5 mg/ml时，与膜联蛋白V偶联步骤的放射化学分步产率高达70%。用化疗药物依托泊苷治疗的癌细胞与未治疗的细胞相比，F-18标记的膜联蛋白V的结合增加了88%。我们得出结论，[F-18]标记的膜联蛋白V可以很容易地通过膜联蛋白V与[F-18]SFB偶联制备，并且正电子发射化合物在检测细胞凋亡方面具有生物活性。(C) 2004爱思唯尔公司版权所有。
The clinical response to antitumor therapy is measured using imaging, such as CT or MRI, 6-12 weeks following chemotherapy treatment. The images at that time reflect both tumor cell death and new growth. Therefore, the amount of tumor cell death caused by chemotherapy cannot be efficiently quantified with current imaging modalities. A quantitative measurement of tumor cell death immediately following chemotherapy is needed to help validate both new agents and to optimize administration of existing therapies. Annexin V is a 36kD protein that binds to exposed phosphatidylserine (PS) on dying cells. In order to synthesize a probe that can detect cell death in vivo, the positron emitter F-18 was conjugated to annexin V via the compound N- succinimidyl-4-[F-18]fluorobenzoate, [F-18]SFB. The decay corrected radiochemical yield of F-18 labeled annexin V from F-18 fluoride was 17.6+/-5.6 % (n=4) in three hours. The stepwise radiochemical yield of the conjugation step with annexin V was as high as 70% when a protein concentration of 5 mg/ml was used. Cancer cells treated with the chemotherapeutic agent, etoposide, showed an 88% increase in the binding of F-18 labeled annexin V compared to untreated cells. We conclude that [F-18] labeled annexin V can be readily prepared by the conjugation of annexin V with [F-18]SFB and that the positron-emitting compound is biologically active in detecting apoptosis. (C) 2004 Elsevier Inc. All rights reserved.