Radiopharmaceuticals for Tumor Imaging and Photodynamic Therapy

描述(申请人提供)：体内特定类型肿瘤的非侵入性分子成像，随之而来的是量身定制的医学发明，正在成为癌症治疗的新前沿。我们的初步研究表明，抗肿瘤的卟啉化合物(例如，HPPH，一种叶绿素-a类似物)可以用作将放射性核素输送到肿瘤的载体。生物分布结果表明，药物在肿瘤/非肿瘤组织中的摄取率与时间和肿瘤大小有关。肿瘤成像的时间被发现是一个重要的参数，因为随着时间的推移，光敏剂从肿瘤组织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，用寿命更长的同位素如LN-111取代“到(半衰期6小时)”可以提供一种有用的扫描剂。在初步的体内研究中，与HPPH相比，相应的非放射性In(111)络合物在第3天产生了10倍的体内光敏效应，而没有明显的皮肤光毒性。在平行的研究中，我们能够将3-碘苯醚基团转化为相应的高特异性的1-124类似物。在体外和体内的初步筛选中，该化合物(非放射性类似物)被发现是相当有效的。在与[F]FDG的对比研究中，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制剂(双功能制剂)的另一种方法可能是用那些显示出更高的肿瘤与非肿瘤比率并在750-800 nm附近产生长波吸收的化合物来取代HPPH(该波长的光治疗可用于治疗大型肿瘤和深埋肿瘤)。结合物的比较研究将包括：肿瘤体内反射光谱摄取、肿瘤成像、体外和体内PDT疗效、皮肤光毒性、生物分布研究和一般毒性。肿瘤显像剂或改进的光动力学治疗剂(S)本身的发展是重要的一步，但双功能试剂(SPECT/PDT或PET/PDT)为随后的靶向治疗提供了诊断性全身扫描的可能性。

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.