Shared Instrumentation Grant

描述（由申请人提供）：申请资金用于为约翰霍普金斯大学购买实时带电粒子自放射成像仪。该设备将辅助分子靶标检测（全身和组织分布，靶标特异性），放射配体开发（药代动力学和药理学特异性，与蛋白质表达的相关性），放射药物剂量测定（全身和组织剂量测定）。蛋白质调控、细胞增殖、组织代谢和血管化的研究也将得到加强。Biospace Measures Beta Imager 2000Z带电粒子成像系统（2000Z）因其多重优势而被选中。它的大视野将允许全身放射自显影，它的高灵敏度将允许对H-3标记配体进行成像。利用2000Z正电子，可以在60至500微米的空间分辨率下检测到与各种放射性示踪剂相关的β、α和电子，检测阈值为0.007 cpm/mm2，检测时间为3H，效率高达90%。在104的动态范围内，成像仪的线性度在2%以内。2000Z成像仪允许同时检测两种或三种同位素，使用衰变时间差或带电粒子能量进行区分。多重标记开辟了新的应用，同时定量几个分子靶标，这将支持药物和放射性配体选择性研究。数据以列表模式收集，从而可以回顾性地检查在不同收集时间段获得的图像。该装置可以实时显示采集到的图像，从而消除曝光不足和曝光过度。相关性：2000Z成像仪将被NIH资助的一个主要研究小组定期使用。每个纳入的项目都有强大的NIH资助，并且与公共卫生相关。它们包括开发治疗癌症的放射性药物和放射方法，以及改进检测癌症和心血管疾病的诊断方法。该仪器将对新的放射配体的开发以及PET和SPECT新的量化算法的验证产生重大影响。它对于发展基于粒子和粒子辐射的放射性核素疗法也至关重要，并将对配体和同位素的选择、递送方法、剂量学估计和治疗反应的测量产生重大影响。

DESCRIPTION (provided by applicant): Funds are requested for acquisition of a real time charged particle autoradiographic imager for the Johns Hopkins University. This device will assist molecular target detection (whole body and tissue distribution, target specificity), radioligand development (pharmacokinetics and pharmacological specificity, correlation with protein expression), radiopharmaceutical dosimetry (both whole body and tissue dosimetry). Investigations of protein regulation, cell proliferation, tissue metabolism and vascularization will also be enhanced. The Biospace Measures Beta Imager 2000Z charged particle imaging system (2000Z) has been selected because of its multiple advantages. Its large field of view will permit whole body autoradiography and its high sensitivity will permit imaging of H-3 labeled ligands. With the 2000Z positrons, betas, alphas and electrons associated with various radiotracers can be detected at spatial resolutions of 60 to 500 micrometer, at a detection threshold of 0.007 cpm/mm2 for 3H and with an efficiency as high as 90%. Linearity of the imager is within 2 % over the dynamic range of 104. The 2000Z Imager allows simultaneous detection of two or three isotopes using decay time differences or charged particle energies for discrimination. Multiple labeling opens up new applications with simultaneous quantification of several molecular targets at a time which will support drug and radioligand selectivity studies. Data are collected in list mode making it possible to retrospectively examine images acquired over different collection time-periods. The device can display the collected image in real-time, thereby eliminating under and over-exposures. RELEVANCE: The 2000Z Imager will be regularly employed by a major group of NIH funded researchers. Each of the included projects have strong NIH funding and are relevant to public health. They cover development of radiopharmaceuticals and radiation methodologies to treat cancer and diagnostic methods for improved detection of cancer and cardiovascular diseases. This instrument will have a strong impact on the development of new radioligands and for validation of new quantification algorithms for PET and SPECT. It will be also essential in the development of radionuclide therapies based on beta and alpha particle radiation and will significantly impact selection of ligands and isotopes, methods of delivery, estimation of dosimetry, and measurement of treatment response.