Non-oncologic applications of radiolabeled peptides in nuclear medicine.

Abstract

Radiolabeled peptides have been investigated for diagnostic imaging in a variety of non-oncologic diseases. For imaging thromboembolic disease, peptides which bind to various components of thrombi have been tested. For targeting the fibrin component of thrombi, peptide analogues of fibrin or fragments of fibronectin which have a distinct binding domain for fibrin have been studied. For targeting activated platelets within thrombi, linear and cyclic peptide antagonists of the glycoprotein IIb/IIIa receptor on platelets have been studied, as well as naturally occurring antagonists of this receptor which are found in venoms. Analogues of laminin and thrombospondin which bind to other receptors on platelets have also been tested. There is an approach which uses a peptide to target thrombin which is sequestered within a fibrin clot. Another area of investigation has been to develop an improved radiopharmaceutical for imaging sites of infection and/or inflammation. Peptides which would bind to leukocytes in vivo, such as antagonists to the tuftsin receptor, chemotactic peptides, interleukin-8, or a platelet factor 4 analogue, have been radiolabeled for this purpose. These agents would enable imaging of both infection and inflammation. Development of a radiopharmaceutical for specifically imaging infection has focused on antimicrobial peptides such as human neutrophil defensin, ubiquicidin, human lactoferrin and alafosfalin, which are expected to bind selectively to microorganisms and not to leukocytes. Radiolabeled peptides are also being explored as agents for assessing unstable atherosclerotic plaque (endothelin), amyloid deposits (amyloid beta peptides), and the consequences of diabetes mellitus (human C-peptide).