新型强效碘代和氟代放射性示踪剂的合成、放射性碘标记及体内筛选作为黑色素瘤成像和治疗探针。

Synthesis, radioiodination and in vivo screening of novel potent iodinated and fluorinated radiotracers as melanoma imaging and therapeutic probes.

机构信息

Clermont Université, Université d'Auvergne, BP 10448, F-63000 Clermont-Ferrand, France.

出版信息

Eur J Med Chem. 2013 May;63:840-53. doi: 10.1016/j.ejmech.2012.11.047. Epub 2013 Mar 24.

DOI:10.1016/j.ejmech.2012.11.047

Abstract

In order to develop new iodinated and fluorinated matched-pair radiotracers for Single-Photon Emission Computed Tomography (SPECT)/Positron Emission Tomography (PET) imaging and targeted radionuclide therapy of melanoma, we successfully synthesized and radiolabelled with iodine-125 seven new derivatives, starting from our previously described lead structure 3. The relevance of these radiotracers for gamma scintigraphic imaging of melanoma in rodent was assessed. The tumoural radioactivity uptake was most often high and specific even at early time points (12.1-18.3% ID/g at 3 h p.i. for [(125)I]39-42) and a fast clearance from the non-target organs was observed. Also, calculated effective doses that could be delivered to tumours when using corresponding [(131)I]-labelled analogues were generally higher than 100 cGy/MBq injected (98.9-150.5 cGy/MBq for [(131)I]39-42). These results make compounds 39-42 suitable candidates for (i) PET imaging of melanoma after labelling with fluorine-18 and (ii) targeted radionuclide therapy of disseminated melanoma after labelling with iodine-131.

摘要

为了开发用于单光子发射计算机断层扫描（SPECT）/正电子发射断层扫描（PET）成像以及黑色素瘤靶向放射性核素治疗的新型碘代和氟代匹配对放射性示踪剂，我们成功地合成并放射性标记了 7 种新的衍生物，这些衍生物都是以我们之前描述的先导结构 3 为基础的。评估了这些放射性示踪剂用于啮齿动物黑色素瘤伽马闪烁成像的相关性。即使在早期时间点（注射后 3 小时的放射性摄取率为 12.1-18.3% ID/g，用于 [(125)I]39-42），肿瘤的放射性摄取通常也很高且具有特异性，并且可以观察到从非靶器官快速清除。此外，当使用相应的 [(131)I]-标记类似物时，可以递送至肿瘤的计算有效剂量通常高于 100 cGy/MBq 注射（对于 [(131)I]39-42，为 98.9-150.5 cGy/MBq）。这些结果使得化合物 39-42 成为（i）用氟-18 标记后的黑色素瘤 PET 成像以及（ii）用碘-131 标记后的播散性黑色素瘤靶向放射性核素治疗的合适候选物。