Radiopharmaceuticals for Tumor Imaging and Photodynamic 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学发明正在成为癌症治疗的新前沿。我们的初步研究表明，tumoravid卟啉为基础的化合物（如HPPH，叶绿素-a类似物）可以用作车辆提供放射性核素到肿瘤。生物分布结果表明，药物的肿瘤/非肿瘤摄取比依赖于时间和肿瘤大小。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比大多数非肿瘤组织慢。因此，对于进一步的研究，用更长寿命的同位素如In-111代替In-111（半衰期6小时）可以提供有用的扫描剂。在初步的体内研究相比，HPPH，相应的非放射性In（III）配合物产生了10倍的增加，在体内光敏化的功效，没有显着的皮肤光毒性的第3天。在平行研究中，我们能够以高特异性将3-碘苄基醚基团转化为相应的1-124类似物。在初步的体外和体内筛选中，发现该化合物（非放射性类似物）非常有效。在与[ F]FDG的比较研究中，相应的1-124光敏剂显示出更好的肿瘤特异性（见初步结果）。开发改进的肿瘤成像和光疗剂（双功能剂）的另一种方法可以是用那些表现出显著更高的肿瘤与非肿瘤比率并在750-800 nm附近产生长波长吸收的化合物代替HPPH（在该波长下的光治疗可用于治疗大肿瘤和那些深位的肿瘤）。结合物的比较研究将包括：通过体内反射光谱法的肿瘤摄取、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。

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.