کد مقاله کد نشریه سال انتشار مقاله انگلیسی ترجمه فارسی نسخه تمام متن
5528952 1401670 2018 9 صفحه PDF سفارش دهید دانلود کنید
عنوان انگلیسی مقاله
[99mTc]duramycin for cell death imaging: Impact of kit formulation, purification and species difference
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
[99mTc]duramycin for cell death imaging: Impact of kit formulation, purification and species difference
چکیده انگلیسی

Introduction[99mTc]duramycin is a SPECT tracer for cell death imaging. We evaluated the impact of kit formulation, purification and species difference on the pharmacokinetic profile and cell death targeting properties of [99mTc]duramycin in order to define the optimal conditions for (pre-)clinical use.MethodsThree kits were prepared (A: traditional formulation, B: containing 1/3 of ingredients, C: containing HYNIC-PEG12-duramycin). Following labeling, the kits were used without purification, or with SPE or HPLC purification. The pharmacokinetic profile was evaluated in mice and rats at 24 h post tracer injection (p.i.). Non-specific accumulation of [99mTc]duramcyin was studied by μSPECT imaging in chemotherapy treated COLO205 tumor bearing mice pre-treated with cold duramycin (0.01-50 μg). Cell death targeting ability of the kits displaying the best pharmacokinetic profile was compared in a treatment response study in COLO205 tumor bearing mice treated with conatumumab (anti-DR5 antibody).ResultsHPLC purification of kit prepared [99mTc]duramycin and reducing the amount of kit ingredients resulted in the best pharmacokinetic profile with low accumulation in liver, spleen and kidneys. The use of PEGylated [99mTc]duramycin required longer circulation times (> 4 h pi) to obtain good imaging characteristics. Pre-treatment with duramycin significantly decreased tracer uptake in chemotherapy treated tumors in a dose-dependent manner. A blocking dose of 50 μg significantly increased non-specific accumulation in liver and spleen. Non-specific accumulation of [99mTc]duramycin was however demonstrated to be species dependent. HPLC purified kit A (5.21 ± 1.71 %ID/cc) and non-purified kit B (1.68 ± 0.46 %ID/cc) demonstrated a significant increase in tumor uptake compared to baseline following conatumumab treatment.ConclusionsTo obtain [99mTc]duramycin with favorable imaging characteristics for cell death imaging in mice [99mTc]duramycin needs to be prepared with high specific activity by applying HPLC purification. The need for HPLC purification appears to be a species dependent phenomenon and might therefore not be required for clinical translation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Nuclear Medicine and Biology - Volume 56, January 2018, Pages 1-9
نویسندگان
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