Innis R B, Malison R T, al-Tikriti M, Hoffer P B, Sybirska E H, Seibyl J P, Zoghbi S S, Baldwin R M, Laruelle M, Smith E O
West Haven VA Medical Center, Connecticut.
Synapse. 1992 Mar;10(3):177-84. doi: 10.1002/syn.890100302.
We used the reversibly binding D2 dopamine receptor radioligand [123I]IBZM (iodobenzamide) to test whether the endogenous neurotransmitter dopamine competes in vivo for radiotracer binding measured with single photon emission computed tomography (SPECT). In a series of nonhuman primate experiments (n = 27), the effects of temperature, amphetamine, haloperidol, and reserpine on brain uptake of [123I]IBZM were measured. Specific brain uptake of [123I]IBZM reached a peak by 100 min postinjection of radioligand and demonstrated a gradual, apparent "steady-state" washout over the next 2 hr. Brain uptake was temperature dependent, with rates of washout of specifically bound radioligand greater under normothermic conditions (26%/hr: core body temperature 35-37 degrees C) than under conditions of controlled hypothermia (11%/hr; 32-34 degrees C). Given the greater retention of radioactivity, low-temperature conditions were used in all other experiments. Administration of haloperidol (0.02 mg/kg IV) during the period of apparent steady state resulted in a dramatic increase in washout (60%/hr; p less than 0.0001), consistent with its potent D2 receptor antagonist properties. d-Amphetamine (1.0 mg/kg IV), which has negligible affinity for the D2 receptor but mediates the release of endogenous stores of dopamine, also enhanced washout (34%/hr; p less than 0.0005). Reserpine pretreatment at doses (1.0 mg/kg) sufficient to cause greater than 90% depletion of striatal dopamine levels blocked this amphetamine-enhanced washout (10%/hr; p less than 0.05). Reserpine did not block the increased washout induced by the direct-acting D2 receptor antagonist haloperidol. These results are consistent with the hypothesis that endogenous dopamine may effectively compete for radioligand binding in vivo in neuroreceptor imaging studies using PET and SPECT.
我们使用可逆结合的D2多巴胺受体放射性配体[123I]碘苄酰胺（iodobenzamide）来测试内源性神经递质多巴胺在体内是否会竞争通过单光子发射计算机断层扫描（SPECT）测量的放射性示踪剂结合。在一系列非人类灵长类动物实验（n = 27）中，测量了温度、苯丙胺、氟哌啶醇和利血平对[123I]碘苄酰胺脑摄取的影响。[123I]碘苄酰胺的特异性脑摄取在注射放射性配体后100分钟达到峰值，并在接下来的2小时内呈现出逐渐明显的“稳态”清除。脑摄取依赖于温度，在正常体温条件下（26%/小时；核心体温35 - 37摄氏度），特异性结合放射性配体的清除率高于控制性低温条件下（11%/小时；32 - 34摄氏度）。鉴于放射性的保留更多，在所有其他实验中都使用了低温条件。在明显的稳态期间静脉注射氟哌啶醇（0.02 mg/kg）导致清除率显著增加（60%/小时；p小于0.0001），这与其强效的D2受体拮抗剂特性一致。d - 苯丙胺（1.0 mg/kg静脉注射）对D2受体的亲和力可忽略不计，但介导内源性多巴胺储备的释放，也增强了清除率（34%/小时；p小于0.0005）。剂量为（1.0 mg/kg）足以导致纹状体多巴胺水平耗竭超过90%的利血平预处理可阻断这种苯丙胺增强的清除率（10%/小时；p小于0.05）。利血平并未阻断由直接作用的D2受体拮抗剂氟哌啶醇诱导的清除率增加。这些结果与以下假设一致，即在使用PET和SPECT的神经受体成像研究中，内源性多巴胺可能在体内有效竞争放射性配体结合。
