F-18 FDG Peptides for Pretargeted PET Imaging of Pancrea

用于胰腺预靶向 PET 成像的 F-18 FDG 肽

• 批准号: 6990639
• 负责人: William John McBride
• 金额: $ 13.43万
• 依托单位: IMMUNOMEDICS, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6990639
• 关键词: antibody; antigen antibody reaction; bioimaging /biomedical imaging; clinical research; deoxyglucose; diagnosis design /evaluation; early diagnosis; fluorine; high performance liquid chromatography; human subject; method development; neoplasm /cancer diagnosis; pancreas imaging /visualization; pancreas neoplasms; peptides; positron emission tomography; radionuclides; tumor antigens

DESCRIPTION (provided by applicant): Our primary interest is to develop an imaging method based on bispecific antibody (bsMAb) pretargeting used in combination with F-18 labeled peptides. Such a method would improve the specificity for PET imaging based on the bsMAb's reactivity with either tumor antigens or other markers. This imaging method would take advantage of excellent sensitivity of PET and the high tumor to non-tumor ratios provided by bsMab pretargeting. We have previously described a novel bsMAb pretargeting system based on the hapten binding specificity of an antibody directed to histamine-succinyl-glycine (HSG; 32). Using this system, radiolabeled peptides can be prepared with a variety of radioisotopes for use in imaging and therapy. This pretargeting system has excellent tumor uptake and high tumor/nontumor ratios within 1-3 hours of the peptide injection, and has substantially less renal uptake than directly radiolabeled antibody fragments (e.g., Fab' or scFv). Given the proven success of this pretargeting system, the primary goal of this Phase I application is to examine methods for preparing peptides suitable for use with F-18, the most commonly used radionuclide for PET imaging. The main focus will be to choose a linker to attached the F-18 to a peptide through the F-18 labeled molecule 4-[F-18]fluorobenzaldehyde. Several potential synthetic pathways will be examined with respect to the facile use, yield of product, specific activity, stability, retention of binding to the anti-hapten component of the bsMAb and ease of purification. The targeting peptide will carry two HSG haptens to stabilize binding on the tumor cell surface. Most of the preclinical work has been done with a bsMab that binds to the colo-rectal tumor marker carcinoembryonic antigen and HSG. The proof of principal for this work will be tested using a bsMAb that targets the human pancreatic tumor antigen, MUC1 and HSG. The goal is to help improve the early detection and diagnosis of pancreatic cancer as well as determine the extent of the disease. It is anticipated that following successful synthesis a SBIR Phase II grant would support the optimization, automation and the scale-up of the 4-[F-18]fluorobenzaldehyde conjugation to the peptide to a commercial scale. It would also support the preclinical targeting, synthesis of new peptide derivatives to optimize excretion, serum stablity and safety studies in animals that would be needed before this agent goes into the clinic.

描述（由申请人提供）： 我们的主要兴趣是开发一种基于双特异性抗体（bsMAb）预靶向与F-18标记肽组合使用的成像方法。这种方法将基于bsMAb与肿瘤抗原或其他标志物的反应性来提高PET成像的特异性。这种成像方法将利用PET的优异灵敏度和bsMab预靶向提供的高肿瘤与非肿瘤比率。我们先前已经描述了一种新的bsMAb预靶向系统，其基于针对组胺-琥珀酰-甘氨酸（HSG; 32）的抗体的半抗原结合特异性。使用该系统，可以用各种放射性同位素制备放射性标记的肽，用于成像和治疗。该预靶向系统在肽注射的1-3小时内具有优异的肿瘤摄取和高肿瘤/非肿瘤比率，并且具有比直接放射性标记的抗体片段（例如，Fab'或scFv）。鉴于这种预靶向系统已被证明是成功的，该I期应用的主要目标是检查用于制备适合与F-18（PET成像中最常用的放射性核素）一起使用的肽的方法。主要的焦点将是选择一个连接器，通过F-18标记的分子4-[F-18]氟苯甲醛将F-18连接到肽。将检查几种潜在的合成途径，包括简便使用、产物产率、比活性、稳定性、与bsMAb抗半抗原组分结合的保留和纯化的容易性。靶向肽将携带两个HSG半抗原以稳定在肿瘤细胞表面上的结合。大多数临床前工作都是用与结肠直肠肿瘤标志物癌胚抗原和HSG结合的bsMab完成的。将使用靶向人胰腺肿瘤抗原、MUC 1和HSG的bsMAb检测这项工作的主要证据。目的是帮助改善胰腺癌的早期检测和诊断，以及确定疾病的程度。预计在成功合成后，SBIR II期资助将支持4-[F-18]氟苯甲醛与肽缀合的优化、自动化和规模扩大至商业规模。它还将支持临床前靶向，合成新的肽衍生物，以优化排泄，血清稳定性和动物安全性研究，这是该药物进入临床之前所需的。

项目成果

A novel facile method of labeling octreotide with (18)F-fluorine.

• DOI: 10.2967/jnumed.109.066902
• 发表时间: 2010-03
• 期刊: Journal of nuclear medicine : official publication, Society of Nuclear Medicine
• 作者: Laverman P;McBride WJ;Sharkey RM;Eek A;Joosten L;Oyen WJ;Goldenberg DM;Boerman OC
• 通讯作者: Boerman OC

Quantitative immuno-SPECT monitoring of pretargeted radioimmunotherapy with a bispecific antibody in an intraperitoneal nude mouse model of human colon cancer.

在人结肠癌腹膜内裸鼠模型中使用双特异性抗体进行预靶向放射免疫治疗的定量免疫 SPECT 监测。

• DOI: 10.2967/jnumed.112.106278
• 发表时间: 2012
• 期刊: Journal of nuclear medicine : official publication, Society of Nuclear Medicine
• 作者: Schoffelen,Rafke;vanderGraaf,WinetteTA;Sharkey,RobertM;Franssen,GerbenM;McBride,WilliamJ;Chang,Chien-Hsing;Bos,DesiréeL;Goldenberg,DavidM;Oyen,WimJG;Boerman,OttoC
• 通讯作者: Boerman,OttoC

Development of an imaging-guided CEA-pretargeted radionuclide treatment of advanced colorectal cancer: first clinical results.

开发成像引导的CEA-PRETARTARGITARGITAL核素治疗晚期结直肠癌：首次临床结果。

• DOI: 10.1038/bjc.2013.376
• 发表时间: 2013-08-20
• 期刊: British journal of cancer
• 影响因子: 8.8
• 作者: Schoffelen R;Boerman OC;Goldenberg DM;Sharkey RM;van Herpen CM;Franssen GM;McBride WJ;Chang CH;Rossi EA;van der Graaf WT;Oyen WJ
• 通讯作者: Oyen WJ

Pretargeted immuno-positron emission tomography imaging of carcinoembryonic antigen-expressing tumors with a bispecific antibody and a 68Ga- and 18F-labeled hapten peptide in mice with human tumor xenografts.

• DOI: 10.1158/1535-7163.mct-09-0862
• 发表时间: 2010-04
• 期刊: Molecular cancer therapeutics
• 影响因子: 5.7
• 作者: Schoffelen R;Sharkey RM;Goldenberg DM;Franssen G;McBride WJ;Rossi EA;Chang CH;Laverman P;Disselhorst JA;Eek A;van der Graaf WT;Oyen WJ;Boerman OC
• 通讯作者: Boerman OC