Seibyl J P, Zea-Ponce Y, Brenner L, Baldwin R M, Krystal J H, Offord S J, Mochoviak S, Charney D S, Hoffer P B, Innis R B
Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT 06520-8042, USA.
J Nucl Med. 1996 Jan;37(1):11-5.
PET has shown that dose-dependent in vivo occupancy of dopamine receptors by antipsychotic drugs is associated with clinical response to antipsychotic agents and the production of extrapyramidal side effects. We studied the feasibility of administering [123I]IBZM as a bolus plus continuous infusion over 8 hr to achieve unchanging regional brain activity levels, and the application of [123I]IBZM continuous infusion to examine the effects of the antipsychotic agent RWJ-37796, on striatal activity in humans.
Five healthy male subjects received a bolus of [123I]IBZM followed by a continuous infusion at a bolus (mCi):infusion (mCi/hr) ratio of 6:1. Serial SPECT images were obtained every 2-3 min for a total of 8 hr with a 1-2 hr break in the scanning session. Serial venous blood samples were obtained every 30 min for the duration of the study. All five subjects achieved unchanging plasma [123I]IBZM and striatal brain-activity levels over the 300-420 min postinitiation of tracer infusion. Two subjects achieved flat brain time-activity curves later than the others, suggesting the bolus-to-infusion ratio was slightly high. An additional six healthy male subjects received a similar bolus plus constant infusion of [123I]IBZM. RWJ-37796 (0.04 mg/kg) was administered intravenously 157 +/- 13.7 min after the initiation of [123I]IBZM infusion. Serial SPECT brain images, serum prolactin and extrapyramidal side effect ratings were obtained for an additional 330 min.
All six subjects demonstrated rapid and marked reduction of striatal activity following RWJ-37796 without return of striatal activity to baseline levels over the 5.5 hr of continued [123I]IBZM administration. Estimated receptor occupancy by RWJ-37796 was 57% +/- 5% (range 47%-67%). Prolactin was only transiently increased in all subjects by 1054% +/- 1084% over baseline. One subject experienced moderate extrapyramidal symptoms (akasthisia) during RWJ-37796 injection.
SPECT imaging during continuous [123I]IBZM infusion provides a powerful within-scan method for determining both temporal binding characteristics and receptor occupancy of striatal dopamine receptors by antipsychotic agents.
正电子发射断层扫描（PET）显示，抗精神病药物对多巴胺受体的体内剂量依赖性占据与抗精神病药物的临床反应及锥体外系副作用的产生有关。我们研究了静脉推注加8小时持续输注[123I]碘苄胍（[123I]IBZM）以实现区域脑活动水平不变的可行性，以及应用[123I]IBZM持续输注来研究抗精神病药物RWJ - 37796对人体纹状体活动的影响。
5名健康男性受试者接受一次[123I]IBZM静脉推注，随后以推注（毫居里）：输注（毫居里/小时）比例为6:1进行持续输注。每隔2 - 3分钟获取一系列单光子发射计算机断层扫描（SPECT）图像，共8小时，扫描过程中有1 - 2小时的休息时间。在研究期间每隔30分钟采集一系列静脉血样。所有5名受试者在示踪剂输注开始后的300 - 420分钟内血浆[123I]IBZM和纹状体脑活动水平保持不变。两名受试者的脑时间 - 活动曲线比其他受试者更晚趋于平稳，提示推注与输注比例略高。另外6名健康男性受试者接受了类似的[123I]IBZM推注加持续输注。在[123I]IBZM输注开始后157±13.7分钟静脉注射RWJ - 37796（0.04mg/kg）。在接下来的330分钟内获取一系列SPECT脑图像、血清催乳素水平及锥体外系副作用评分。
所有6名受试者在给予RWJ - 37796后纹状体活动迅速且显著降低，在持续给予[123I]IBZM的5.5小时内纹状体活动未恢复至基线水平。RWJ - 37796的受体占有率估计为57%±5%（范围47% - 67%）。所有受试者的催乳素仅短暂升高，比基线水平升高1054%±1084%。一名受试者在注射RWJ - 37796期间出现中度锥体外系症状（静坐不能）。
在[123I]IBZM持续输注期间进行SPECT成像提供了一种强大的扫描内方法，可用于确定抗精神病药物对纹状体多巴胺受体的时间结合特性和受体占有率。
