کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1394525 1501166 2012 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
99mTc(I)/Re(I) tricarbonyl complexes for in vivo targeting of melanotic melanoma: Synthesis and biological evaluation
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
99mTc(I)/Re(I) tricarbonyl complexes for in vivo targeting of melanotic melanoma: Synthesis and biological evaluation
چکیده انگلیسی

The 99mTc (I) tricarbonyl complexes fac-[99mTc(κ3-L)(CO)3] (Tc1–Tc6) containing N-ethylpyrrolidine and N,N-diethylethylamine groups for melanin binding, were evaluated in vitro and in vivo as radioactive probes for the targeting of melanotic melanoma. Aiming at the modification of their size, topology and lipophilicity, Tc1–Tc6 were obtained based on an S,N,O-donor bifunctional chelator (BFC) derived from cysteamine and on pyridyl- and pyrazolyl-containing N,N,O-donor BFCs. Tc1–Tc6 were chemically identified by HPLC comparison with the Re congeners (Re1–Re6) that were synthesized at the macroscopic level and fully characterized by common analytical techniques. With the exception of Tc5 and Tc6, these 99mTc complexes are moderately lipophilic, and bind to melanin with moderate to high affinity (23–87%). The cell uptake of Tc1–Tc6, expressed as a percentage of total activity per million cells, spanned between 0.86 and 21.02% for the melanotic B16-F1 cell line and between 0.49% and 13.58% for the amelanotic A375 cell line. In the B16-F1 cell line, Tc1, Tc3 and Tc4 showed moderate cellular uptake values (>10% at 4 h of incubation). In the amelanotic A375 cell line, only Tc4 has shown a moderate cell uptake (>10% at 4 h of incubation), with all the other compounds displaying a relatively poor uptake, i.e. inferior to 5%. Competition studies with haloperidol have shown that the involvement of sigma receptors in cellular uptake and retention is likely to occur for Tc4. Complex Tc1, stabilized with the S,N,O-donor BFC and containing a N,N-diethylethylamine group, presented the most promising biological profile for in vivo targeting of melanoma, showing a moderate tumor uptake of 2.17% ID/g at 1 h p.i in a B16-F1 melanoma-bearing mouse and rather favorable target/non-target ratios with values as high as 16.9 and 5.2 for tumor/muscle and tumor/blood ratios, respectively.

Figure optionsDownload as PowerPoint slideHighlights
► New 99mTc (I) tricarbonyl complexes for in vivo imaging of melanotic melanoma.
► Lipophilic complexes presenting a moderate to high affinity towards melanin.
► A complex with a (S,N,O)-chelator showed an encouraging biological profile.
► Clear detection of a murine melanoma tumor with high imaging contrast.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 50, April 2012, Pages 350–360
نویسندگان
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