Fullerene Immunoconjugates for Cancer Imaging and Treatment

描述（由申请人提供）：在这个由TDA研究中心、莱斯大学和M.D.安德森癌症中心合作的项目中，我们将开发新的金属富勒烯-紫杉醇抗体偶联物，用于联合癌症成像和治疗。富勒烯是一种无毒的碳笼分子，具有丰富的衍生化化学作用，可用于偶联药物分子，生成治疗性前药。内源性金属富勒烯Gd@C60在先前的研究中已被证明可以有效地作为T1显像剂，包括用于细胞标记。Gd@C60提供了一个安全的造影剂平台，缺乏游离Gd3+毒性的潜力，因为内源性Gd隔离的稳定性非常高，在生理条件下不会受到损害。我们将化学偶联紫杉醇基团到Gd@C60衍生物，形成一个新的联合治疗/显像剂前药。使用Gd@C60-paclitaxel偶联物，将形成具有抗gp240黑色素瘤抗体ZME-018的新免疫偶联物，并在体外测试细胞摄取，MRI造影剂功效和对黑色素瘤癌细胞的细胞毒性。抗体靶向与治疗性MR显像剂相结合的策略将改善黑色素瘤的诊断、治疗和患者预后，并具有同时靶向多种药物治疗癌细胞的潜力。

DESCRIPTION (provided by applicant): In this collaborative project between TDA Research, Rice University and M.D. Anderson Cancer Center, we will develop new metallofullerene-taxol-antibody conjugates for combined cancer imaging and treatment. Fullerenes are non-toxic carbon cage molecules with a rich derivatization chemistry useful for conjugating drug molecules, to generate therapeutic prodrugs. The endohedral metallofullerene Gd@C60 have been shown in prior studies to function effectively as T1 imaging agents, including for cellular labeling. Gd@C60 offers a safe contrast agent platform lacking the potential for free Gd3+ toxicity due to the very high stability of endohedral Gd sequestration, which is not compromised under physiological conditions. We will chemically conjugate paclitaxel groups to a Gd@C60 derivative to form a new combined therapeutic/imaging agent prodrug. Using the Gd@C60-paclitaxel conjugates, new immunoconjugates with the anti-gp240 melanoma antibody ZME-018 will be formed and tested for cellular uptake, for MRI contrast agent efficacy and for cytotoxicity against melanoma cancer cells in vitro. The strategy of combining antibody targeting with a therapeutic MR imaging agent will improve melanoma diagnosis, treatment and patient outcome, and has the potential for targeting multiple drugs to cancerous cells at the same time.