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

Area of Science:

• Cardiovascular Physiology
• Nuclear Medicine
• Pharmacology

Background:

• Accurate measurement of regional myocardial blood flow is critical for diagnosing and managing cardiovascular diseases.
• Ideal flow markers should be completely extracted and retained during transcapillary passage.
• Beta-labeled desmethylimipramine ([3H]DMI) is a nearly ideal flow marker but lacks gamma or positron emission for external detection.

Purpose of the Study:

• To develop a gamma- and positron-emitting tracer for myocardial blood flow imaging.
• To evaluate the suitability of iodinated desmethylimipramine (IDMI) as a flow marker in isolated rabbit hearts.

Main Methods:

• Desmethylimipramine (DMI) was iodinated to create 2-iododesmethylimipramine (IDMI).
• IDMI's lipophilicity, transorgan extraction, and retention were assessed in isolated saline-perfused and blood-perfused rabbit hearts at various flow rates.
• Fractional escape rates and deposition proportionality to flow were determined.

Main Results:

• IDMI demonstrated high transorgan extraction (>99% in saline, 98% in blood) and good retention (>98% at 5 min) in saline-perfused hearts.
• In blood-perfused hearts, retention decreased to 86% at 5 min, with a higher fractional escape rate (up to 2% min-1).
• Despite some washout, regional IDMI deposition remained proportional to regional blood flow for several minutes in both models.

Conclusions:

• Iodinated desmethylimipramine (IDMI) is a lipophilic tracer with high extraction, suitable for myocardial blood flow measurement.
• While retention is lower in blood-perfused hearts, IDMI's flow-proportional deposition allows its use as an externally detectable 'molecular microsphere'.
• IDMI holds promise for in vivo myocardial flow imaging.