Dormehl I, Feinendegen L, Hugo N, Rossouw N, White A
AEC Institute for Life Sciences, University of Pretoria, South Africa.
Nucl Med Commun. 1993 Nov;14(11):998-1004. doi: 10.1097/00006231-199311000-00011.
The use of various animal models for researching radioiodinated fatty acid cardiac metabolism has been proven to be risky. This fact is here confirmed in the higher primate. Six baboons were injected on different occasions with 123I-labelled para and ortho isomers of 15-(iodophenyl) pentadecanoic acid (123I-pPPA and 123I-oPPA, respectively) for dynamic scintigraphy, followed by a Na123I injection at 30 min for blood background correction. Times for maximum myocardial tracer uptake (Tmax), and half-times of clearance (two phases T1/2(1) and T1/2(2)) from biexponential fitting of the time-activity curves proved statistically not different for pPPA and oPPA (P > 0.05). A repeat study at a later stage on the same baboons included pretreatment (2 h pretracer) with a carnitine palmitoyl transferase I inhibitor (Extomoxir; 10 mg kg-1) to block myocardial beta-oxidation. Time-activity curves with Tmax, T1/2(1) and T1/2(2) followed as above and were compared to the initial uninhibited values. Blocking of the carnitine shuttle was demonstrated by significantly increased retention of 123I-pPPA and 123I-oPPA. Thus both the tracers are beta-oxidized in the baboon myocardium, which is different in rat and human studies. In rats both isomers wash out from the myocardium, but 123I-oPPA is not metabolized. In humans the 123I-pPPA is beta-oxidized as with rats, but the 123I-oPPA is retained in the lipid pool of the myocardium. Simultaneous multiple consecutive gated blood pool studies (six of 1 min each) provided encouraging perfusion-related, background corrected images, and corresponding uptake information.
已证明使用各种动物模型研究放射性碘化脂肪酸心脏代谢存在风险。这一事实在高等灵长类动物中得到了证实。六只狒狒在不同时间分别注射了15-(碘苯基)十五烷酸的123I标记的对位和邻位异构体(分别为123I-pPPA和123I-oPPA)用于动态闪烁扫描,随后在30分钟时注射Na123I用于血液本底校正。时间-活性曲线双指数拟合得出的心肌示踪剂摄取最大值时间(Tmax)以及清除半衰期(两个阶段的T1/2(1)和T1/2(2))经统计学分析,pPPA和oPPA并无差异(P>0.05)。对同一批狒狒在后期进行的重复研究包括用肉碱棕榈酰转移酶I抑制剂(依托莫西;10mg/kg)进行预处理(在注射示踪剂前2小时)以阻断心肌β-氧化。按照上述方法记录Tmax、T1/2(1)和T1/2(2)的时间-活性曲线,并与初始未抑制值进行比较。肉碱穿梭的阻断表现为123I-pPPA和123I-oPPA的滞留显著增加。因此,两种示踪剂在狒狒心肌中均进行β-氧化,这与大鼠和人类研究不同。在大鼠中,两种异构体均从心肌中洗脱,但123I-oPPA未被代谢。在人类中,123I-pPPA与大鼠一样进行β-氧化,但123I-oPPA保留在心肌的脂质池中。同步多次连续门控血池研究(每次1分钟,共6次)提供了令人鼓舞的与灌注相关的、经本底校正的图像以及相应的摄取信息。