Radiopharmaceuticals for Tumor Imaging and Photodynamic Therapy

用于肿瘤成像和光动力治疗的放射性药物

• 批准号: 7047684
• 负责人: Ravindra K. Pandey
• 金额: $ 17.79万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-02 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7047684
• 关键词: neoplasm /cancer

DESCRIPTION (provided by applicant): The non-invasive molecular imaging of the specific type of tumor in vivo followed by tailored medical invention is becoming the new frontier in cancer treatment. Our preliminary study indicates that tumoravid porphyrin-based compounds (e.g. HPPH, a chlorophyll-a analog) can be used as a vehicle to deliver the radionuclide to tumors. The biodistribution results indicate that the tumor/non-tumor uptake ration of the drug depend on time and tumor size. The time for tumor imaging was found to be an important parameter because, with time the clearance of the photosensitizer from tumor was found to be slower than most of the non-tumor tissues. Therefore, for further studies replacing "To (half-life 6 hours) with longer-lived isotope such as ln-111 could provide a useful scanning agent. In preliminary in vivo study compared to HPPH, the corresponding nonradioactive In(lll) complex produced a 10-fold increase in in vivo photosensitizing efficacy with no significant skin phototoxicity on day 3. Ina parallel study, we were able to convert the 3-iodobenzylether group into the corresponding 1-124 analog with high specificity. In preliminary in vitro as well as in vivo screening, this compound (non-radioactive analog) was found to be quite effective. In a comparative study with [ F]FDG, the corresponding 1-124 photosensitizer showed better tumor specificity (see Preliminary Results). Another approach for developing an improved tumor-imaging and phototherapy agents (bifunctional agents) could be to replace HPPH with those compounds that exhibit a significantly higher tumor to nontumor ratio and produce long-wavelength absorption near 750-800 nm (light treatment at this wavelength could be useful for treating large tumors and those that are deeply seated. The comparative study of the conjugate will include: tumor uptake by in vivo reflectance spectroscopy, tumor imaging, in vitro and in vivo PDT efficacy, skin phototoxicity, biodistribution study and general toxicity. The development of tumor imaging or improved photodynamic therapy agent(s) by itself represents an important step, but a dual function agent (SPECT/PDT or PET/PDT) provides the potential for diagnostic body scan followed by targeted therapy.

描述（由申请人提供）：体内特定类型肿瘤的非侵入性分子成像以及定制的医疗发明正在成为癌症治疗的新领域。我们的初步研究表明，亲肿瘤卟啉化合物（例如 HPPH，一种叶绿素-a 类似物）可用作将放射性核素递送至肿瘤的载体。生物分布结果表明，药物的肿瘤/非肿瘤摄取比率取决于时间和肿瘤大小。发现肿瘤成像的时间是一个重要参数，因为随着时间的推移，发现光敏剂从肿瘤中的清除速度比大多数非肿瘤组织慢。因此，对于进一步的研究，用较长寿命的同位素（例如 ln-111）替换“To”（半衰期 6 小时）可以提供有用的扫描剂。在与 HPPH 相比的初步体内研究中，产生了相应的非放射性 In(III) 复合物第 3 天，体内光敏功效增加 10 倍，且没有明显的皮肤光毒性。在一项平行研究中，我们能够将 3-碘苄基醚基团转化为相应的基团1-124 类似物具有高特异性。在初步体外和体内筛选中，在与相应的 1-124 光敏剂的比较研究中发现该化合物（非放射性类似物）非常有效。显示出更好的肿瘤特异性（参见初步结果） 开发改进的肿瘤成像和光疗药物（双功能药物）的另一种方法可能是用那些表现出明显更高的肿瘤与非肿瘤比率并产生的化合物代替 HPPH。 750-800 nm 附近的长波长吸收（此波长的光治疗可用于治疗大肿瘤和深层肿瘤。缀合物的比较研究将包括：体内反射光谱的肿瘤摄取、肿瘤成像、体外和体内PDT功效、皮肤光毒性、生物分布研究和一般毒性。肿瘤成像或改进的光动力治疗剂本身的发展代表了重要的一步，但双功能剂（SPECT/PDT 或 PET/PDT）提供了诊断性身体扫描和随后的靶向治疗的潜力。