4-[18F]Fluoro-2-D-methyl-3-mercaptopropanoyl-L-proline

Excerpt

The renin–angiotensin system (RAS) plays a very important role in blood pressure regulation (1-4) in humans. Renin is an enzyme produced in the kidneys and it cleaves circulating angiotensinogen (a protein produced in the liver) to yield angiotensin I, an inactive decapeptide. The angiotensin-converting enzyme (ACE), found primarily in the lung, converts angiotensin I to angiotensin II, an active vasoconstrictor octapeptide. Angiotensin II also stimulates the production of aldosterone from the adrenal glands that promotes sodium and water retention. ACE is also responsible for inactivating bradykinin, a vasodilator (5). RAS and angiotensin II also play a role in interstitial fibrosis, cardiac remodeling and fibrosis, and heart failure (6, 7). It has also been shown that RAS operates in the heart, and the upregulation of this system is related to heart failure (8-10). Inhibition of ACE in patients with heart failure has often resulted in a favorable outcome for the patient (11). In this regard, captopril (2-D-methyl-3-mercaptopropanoyl-L-proline) was developed as an orally active ACE inhibitor and is considered an important drug for the treatment of hypertension. Subsequently, [¹⁸F]fluorocaptopril ([¹⁸F]FCAP) was developed for use with PET (12) to understand the in vivo dynamics of ACE activity.