Application of 99mTechnetium-HYNIC(tricine/TPPTS)-Aca-Bombesin(7-14) SPECT/CT in prostate cancer patients A first-in-man study
Application of 99mTechnetium-HYNIC(tricine/TPPTS)-Aca-Bombesin(7-14) SPECT/CT in prostate cancer patients A first-in-man study
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DOI：
10.1016/j.nucmedbio.2013.05.009
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发表时间：
2013-10-01
影响因子：
3.1
通讯作者：
de Jong, Igle J.
中科院分区：
文献类型：
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作者：
Ananias, Hildo J. K.;Yu, Zilin;de Jong, Igle J.
基本原理：肽蛙皮素（BBN）及其衍生物对在前列腺癌中高度表达的胃泌素释放肽受体（GRPR）表现出高结合亲和力。我们使用BBN基放射性药物（99 m）锝-HYNIC（tricine/TPPTS）-β-蛙皮素（7-14）（Tc-99 m-HABBN）进行首次人体临床试验研究，以评估Tc-99 m-HABBN SPECT/CT检测患者前列腺癌的可行性。8例经活检证实的前列腺癌患者，计划进行根治性前列腺切除术或外照射放疗，治疗前进行HABBN动脉造影和SPECT/CT。采集系列血样以评估血液放射性并测定体内代谢稳定性。测量临床参数，并记录报告的副作用（如果存在）。结果：合成的Tc-99 m-HABBN放射化学产率高，纯度高，比活度高。临床参数无显著变化，无不良或主观副作用。低代谢稳定性观察，小于20%的Tc-99 m-HABBN是完整的30分钟后。GRPR免疫组化染色观察在所有患者的前列腺癌标本。Tc-99 m-HABBN前列腺造影和SPECT/CT在确诊的前列腺癌患者中未检出前列腺癌。Tc-99 m-HABBN SPECT/CT用于前列腺癌的可视化是安全的，但受到人体内意想不到的低代谢稳定性的阻碍。HABBN和低的体内代谢稳定性在这项研究中确定，是惊人的。这个问题需要进一步研究基于肽的放射性药物。(C)2013 Elsevier Inc. All rights reserved.
Rationale: The peptide bombesin (BBN) and its derivatives exhibit high binding affinity for the gastrin-releasing peptide receptor (GRPR), which is highly expressed in prostate cancer. We used the BBN-based radiopharmaceutical (99m)Technetium-HYNIC(tricine/TPPTS)-Aca-Bombesin(7-14) (Tc-99m-HABBN) to perform a first-in-man clinical pilot study to evaluate the feasibility of Tc-99m-HABBN SPECT/CT for detection of prostate cancer in patients.Methods: Eight patients with biopsy-proven prostate cancer who were scheduled for either radical prostatectomy or external beam radiotherapy underwent Tc-99m-HABBN scintigraphy and SPECT/CT prior to treatment. Serial blood samples were taken to assess blood radioactivity and to determine in vivo metabolic stability. Clinical parameters were measured and reported side effects, if present, were recorded. Prostate cancer specimens of all patients were immunohistochemically stained for GRPR.Results: Tc-99m-HABBN was synthesized with high radiochemical yield, purity and specific activity. There were no significant changes in clinical parameters, and there were no adverse or subjective side effects. Low metabolic stability was observed, as less than 20% of Tc-99m-HABBN was intact after 30 min. Immunohistochemical staining for GRPR was observed in the prostate cancer specimens in all patients. Tc-99m-HABBN scintigraphy and SPECT/CT did not detect prostate cancer in patients with proven disease.Conclusions: Tc-99m-HABBN SPECT/CT for visualization of prostate cancer is safe but hampered by an unexpected low in vivo metabolic stability in man. The difference between the excellent in vitro stability of Tc-99m-HABBN in human serum samples determined in our previous study regarding Tc-99m-HABBN and the low in vivo metabolic stability determined in this study, is striking. This issue warrants further study of peptide-based radiopharmaceuticals. (C) 2013 Elsevier Inc. All rights reserved.