Myocardial extraction and retention of 2-iododesmethylimipramine: a novel flow marker

An ideal deposition marker for measuring regional flow is completely extracted during transcapillary passage and permanently retained. beta-Labeled desmethylimipramine ([3H]DMI) is a nearly ideal flow marker. To obtain gamma- and positron-emitting markers, DMI was iodinated to form 2-iododesmethylimipramine (IDMI). IDMI was more lipophilic than DMI. In isolated saline-perfused rabbit hearts its transorgan extraction was greater than 99%; and retention was greater than 98% at 5 min at mean flows of up to 3.5 ml X g-1 X min-1. During washout, the fractional escape rate was less than 0.1% X min-1 and was independent of flow. In isolated blood-perfused rabbit hearts, extraction was still 98%, but retention was as low as 86% after 5 min at a flow of 1.6 ml X g-1 X min-1. The fractional escape rate was up to 2% X min-1 but independent of flow. Despite this relatively rapid loss, regional IDMI deposition remains proportional to regional flow for many minutes. Therefore IDMI is useful as an externally detectable "molecular microsphere" for myocardial flow imaging in vivo.