Pharmacological constraints associated with positron emission tomographic scanning of small laboratory animals
Pharmacological constraints associated with positron emission tomographic scanning of small laboratory animals
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DOI：
10.1007/s002590050211
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发表时间：
1998-02-01
期刊：
影响因子：
--
通讯作者：
Jones, T
中科院分区：
文献类型：
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作者：
Hume, SP;Gunn, RN;Jones, T
为了扫描小鼠感兴趣的小区域，目前正在开发几种高分辨率正电子发射断层扫描（PET）系统。然而，有些方法灵敏度低，需要高剂量的放射性才能达到足以重建小体积的计数统计。利用先前在大鼠脑中测量的三种碳11标记配体的体内解离常数，本文利用简单的饱和动力学来估计放射性和比活性的极限，以最小化受体占用程度并实现最大的放射性配体的特异性结合。考虑到高亲和力配体（体外解离常数类似于0.1 nM；体内类似于5 nmol/kg静脉注射剂量），问题的程度可以举例说明，其中常规产生的比活性水平（类似于100 MBq/nmol）将限制注射到小鼠体内的活性，在1%的受体占用率下，活性类似于0.1 MBq。如果可行的话，新一代高分辨率PET系统需要注入活度为10mbq，那么示踪剂动力学就需要比活度增加100倍。本文强调，如果高分辨率PET被接受为一种可行的方法，以获得小鼠的药理学和生理学上准确的配体受体结合数据，则需要考虑现实可实现的目标。
With the stated aim of scanning small regions of interest in mice, several high-resolution positron emission tomographic (PET) systems are presently under development. Some, however, have low sensitivity and require high doses of radioactivity to achieve count statistics adequate to reconstruct small volumes. Using in vivo dissociation constants for three carbon-11 labelled ligands previously measured in rat brain, the present paper utilises simple saturation kinetics to estimate the limits on radioactivity and specific activity, to minimise the degree of receptor occupancy and achieve maximal specific binding of the radioligand. The extent of the problem is exemplified by considering a high-affinity ligand (dissociation constant in vitro similar to 0.1 nM; in vivo similar to 5 nmol/kg i.v. injected dose), where routinely produced levels of specific activity (similar to 100 MBq/nmol) would limit the activity injected into mice to similar to 0.1 MBq for a 1% receptor occupancy. If, as is feasible, the new generation of high resolution PET systems requires an injected activity >10 MBq, then a >100-fold increase in specific activity would be needed for tracer kinetics to hold. The paper highlights the need to consider realistically achievable goals if high-resolution PET is to be accepted as a viable methodology to acquire pharmacologically and physiologically accurate ligand-receptor binding data in mice.