A dose- and time-controllable syngeneic animal model of breast cancer microcalcification.
A dose- and time-controllable syngeneic animal model of breast cancer microcalcification.
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DOI：
10.1007/s10549-009-0535-6
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发表时间：
2010-07
影响因子：
3.8
通讯作者：
Frangioni, John V.
中科院分区：
文献类型：
--
作者：
Liu, Fangbing;Misra, Preeti;Lunsford, Elaine P.;Vannah, Joanne T.;Liu, Yuxia;Lenkinski, Robert E.;Frangioni, John V.
开发用于检测乳腺癌微钙化的新型诊断剂需要可靠的动物模型。基于我们小组以前的工作，我们假设单次全身注射重组骨形态发生蛋白-2（rBMP-2）可以用于创建这样的模型。编码成熟人BMP-2的cDNA在BL 21（DE 3）细菌中表达，纯化至均一，并重折叠为二聚体。使用C2 C12碱性磷酸酶测定确认生物活性。用99 mTc标记rBMP-2，并在静脉（IV）和腹膜内（IP）注射后定量其生物分布和清除。Fischer 344大鼠携带同系R3230乳腺肿瘤，接受单次腹膜内注射特定剂量的rBMP-2。使用微型单光子发射计算机断层扫描（SPECT）和微型计算机断层扫描（CT）随时间推移对肿瘤微钙化进行定量。rBMP-2在E.大肠杆菌中高水平表达，分离纯度>95%，并重折叠成生物活性二聚体。IV给药后β相半衰期为30.5 min，IP给药后为47.6 min。肾脏排泄是主要清除模式。当肿瘤尚未可触及时，单次IP注射≥ 50 μg rBMP-2导致8/8个R3230肿瘤出现剂量依赖性微钙化。在对照肿瘤中或在注射rBMP-2的动物的正常组织和器官中未发现钙化。肿瘤钙化在注射rBMP-2后2至4周之间逐渐增加。在患有同系乳腺癌的大鼠中单次IP注射rBMP-2将产生剂量依赖性和时间依赖性的微钙化。该动物模型为开发新型乳腺癌诊断放射性示踪剂奠定了基础。
The development of novel diagnostic agents for the detection of breast cancer microcalcifications requires a reliable animal model. Based on previous work from our group, we hypothesized that a single systemic injection of recombinant bone morphogenetic protein-2 (rBMP-2) could be used to create such a model. The cDNA encoding mature human BMP-2 was expressed in BL21(DE3) bacteria, purified to homogeneity, and re-folded as a dimer. Bioactivity was confirmed using a C2C12 alkaline phosphatase assay. rBMP-2 was radiolabeled with 99mTc and its biodistribution and clearance were quantified after both intravenous (IV) and intraperitoneal (IP) injection. Fischer 344 rats bearing syngeneic R3230 breast tumors received a single intraperitoneal injection of rBMP-2 at a specified dose. Tumor microcalcification was quantified over time using micro single-photon emission computed tomography (SPECT) and micro computed tomography (CT). rBMP-2 could be expressed in E. coli at high levels, isolated at >95% purity, and refolded to a bioactive dimer. Beta-phase half-life was 30.5 min after IV administration and 47.6 min after IP administration. Renal excretion was the primary mode of clearance. A single IP injection of ≥ 50 μg rBMP-2 when tumors were not yet palpable resulted in dose-dependent microcalcification in 8 of 8 R3230 tumors. No calcification was found in control tumors, or in normal tissues and organs of animals injected with rBMP-2. Tumor calcification increased progressively between weeks 2 to 4 post-rBMP-2 injection. A single IP injection of rBMP-2 in rats bearing a syngeneic breast cancer will produce dose-dependent and time-dependent microcalcifications. This animal model lays the foundation for the development of novel diagnostic radiotracers for breast cancer.
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影响因子：
4.7
作者：
Langenfeld, EM;Calvano, SE;Langenfeld, J
通讯作者：
Langenfeld, J
DOI：
10.1007/s00432-008-0396-0
发表时间：
2008-11-01
影响因子：
3.6
作者：
Steinert, Susanne;Kroll, Torsten C.;Clement, Joachim H.
通讯作者：
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影响因子：
15
作者：
Bhushan KR;Misra P;Liu F;Mathur S;Lenkinski RE;Frangioni JV
通讯作者：
Frangioni JV
影响因子：
1.6
作者：
Long, SN;Truong, L;Ma, HW
通讯作者：
Ma, HW
影响因子：
5.6
作者：
Scheufler, C;Sebald, W;Hülsmeyer, M
通讯作者：
Hülsmeyer, M