Eisenhut M, Liefhold J
Abt. Nuklearmedizin, Ruprecht-Karls-Universität Heidelberg, F.R.G.
Int J Rad Appl Instrum A. 1988;39(7):639-49. doi: 10.1016/0883-2889(88)90052-4.
Due to the inhibition of beta-oxidation, radiolabeled long-chain fatty acids with substituents in the alkyl chain often can enhance the retention of myocardial radioactivity. In this connection the synthesis and biodistribution of 12 new radioiodinated omega-(p-iodophenyl)fatty acids is described featuring a p-phenylene group as an inhibiting group. Phenyl fatty acid esters were acylated (Friedel-Crafts) with omega-(p-halophenyl)fatty acid chlorides, reduced and hydrolyzed (Wolff-Kishner) to form the omega-(p-halophenyl)-p-phenylene-fatty acid (PHIPA) derivatives. The peak heart uptake and the loss of radioactivity from the myocardium of fasted Sprague-Dawley rats depended on the alkyl-chain length and p-phenylene position. Thus, compared to radioiodinated 15-(p-iodophenyl)pentadecanoic acid (IPPA) some of the 131I labeled PHIPA derivatives with 12, 13 or 14 methylene groups proved to show an about equal initial heart uptake (about 5% inj. dose/g at 2.5 min). This was especially true for those PHIPA derivatives with a p-phenylene moiety close to the carboxylic acid group. The retention of radioactivity in the heart was also significantly prolonged when the p-phenylene group was in this position. Among the PHIPA derivatives investigated, 13-(p[131I]iodophenyl)-3-(p-phenylene)tridecanoic acid (PHIPA 3-10) and 14-(p-[131I] iodophenyl)-4-(p-phenylene)tetradecanoic acid (PHIPA 4-10) showed the most promising characteristics for potential use as new myocardial imaging agents. Both agents showed an initial heart/blood activity ratio of about 10 which increased to 15 after 10-30 min. This high value was maintained for at least 4 h.
由于β-氧化受到抑制，在烷基链上带有取代基的放射性标记长链脂肪酸常常能够提高心肌放射性的保留。在此方面，本文描述了12种新的放射性碘化ω-(对碘苯基)脂肪酸的合成及生物分布，其特征在于以对亚苯基作为抑制基团。苯基脂肪酸酯与ω-(对卤苯基)脂肪酸氯化物进行酰化反应（傅克反应），然后还原并水解（沃尔夫-吉斯纳尔反应）以形成ω-(对卤苯基)-对亚苯基-脂肪酸（PHIPA）衍生物。禁食的斯普拉格-道利大鼠心肌的摄取峰值以及放射性从心肌中的损失取决于烷基链长度和对亚苯基的位置。因此，与放射性碘化15-(对碘苯基)十五烷酸（IPPA）相比，一些带有12、13或14个亚甲基的131I标记的PHIPA衍生物显示出大致相等的初始心肌摄取量（在2.5分钟时约为5%注射剂量/克）。对于那些对亚苯基部分靠近羧基的PHIPA衍生物尤其如此。当对亚苯基处于该位置时，心脏中放射性的保留也显著延长。在所研究的PHIPA衍生物中，13-(对-[131I]碘苯基)-3-(对亚苯基)十三烷酸（PHIPA 3-10）和14-(对-[131I]碘苯基)-4-(对亚苯基)十四烷酸（PHIPA 4-10）显示出作为新型心肌显像剂潜在应用的最有前景的特性。两种药剂的初始心脏/血液活性比约为10，在10 - 30分钟后增加到15。该高值至少维持4小时。
