کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2154865 1090258 2006 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Comparative in vitro and in vivo evaluation of two 64Cu-labeled bombesin analogs in a mouse model of human prostate adenocarcinoma
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Comparative in vitro and in vivo evaluation of two 64Cu-labeled bombesin analogs in a mouse model of human prostate adenocarcinoma
چکیده انگلیسی
Bombesin (BBN), an analog of human gastrin-releasing peptide (GRP), binds to the GRP receptor (GRPR) with high affinity and specificity. Overexpression of GRPR has been discovered in mostly androgen-independent human prostate tissues and, thus, provides a potential target for prostate cancer diagnosis and therapy. We have previously demonstrated the feasibility of the positron emission tomography (PET) imaging using 64Cu-1,4,7,10-tetraazadodecane-N,N′,N″,N″′-tetraacetic acid (DOTA)-[Lys3]BBN to detect GRPR-positive prostate cancer. In this study, we compared the receptor affinity, metabolic stability, tumor-targeting efficacy, and pharmacokinetics of a truncated BBN analog 64Cu-DOTA-Aca-BBN(7-14) with 64Cu-DOTA-[Lys3]BBN. Binding of each DOTA conjugate to GRPR on PC-3 and 22Rv1 prostate cancer cells was evaluated with competitive binding assay using 125I-[Tyr4]BBN as radioligand. In vivo pharmacokinetics was determined on male nude mice subcutaneously implanted with PC-3 cells. Dynamic microPET imaging was performed to evaluate the systemic distribution of the tracers. Metabolic stability of the tracers in blood, urine, tumor, liver and kidney was studied using high-performance liquid chromatography. The results showed that 125I-[Tyr4]BBN has a Kd of 14.8±0.4 nM against PC-3 cells, and the receptor concentration on PC-3 cell surface is approximately 2.7±0.1×106 receptors per cell. The 50% inhibitory concentration value for DOTA-Aca-BBN(7-14) is 18.4±0.2 nM, and that for DOTA-[Lys3]BBN is 2.2±0.5 nM. DOTA-[Lys3]BBN shows a better tumor contrast and absolute tumor activity accumulation compared to DOTA-Aca-BBN(7-14). Studies on metabolic stability for both tracers on organ homogenates showed that 64Cu-DOTA-[Lys3]BBN is relatively stable. This study demonstrated that both tracers are suitable for targeted PET imaging to detect the expression of GRPR in prostate cancer, while 64Cu-DOTA-[Lys3]BBN may have a better potential for clinical translation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Nuclear Medicine and Biology - Volume 33, Issue 3, April 2006, Pages 371-380
نویسندگان
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