Currently Available Radiopharmaceuticals for Imaging Infection and the Holy Grail

Abstract

Infection is ubiquitous. However, its management is challenging for both the patients and the health-care providers. Scintigraphic imaging of infection dates back nearly half a century. The advances in our understanding of the pathophysiology of disease at cellular and molecular levels have paved the way to the development of a large number of radiopharmaceuticals for scintigraphic imaging of infection. These include radiolabeling of blood elements such as serum proteins, white blood cells (WBCs), and cytokines, to name a few. Infectious foci have also been imaged using a radiolabeled sugar molecule by taking advantage of increased metabolic activity in the infectious lesions. Literature over the years has well documented that none of the radiopharmaceuticals and associated procedures that facilitate imaging infection are flawless and acceptable without a compromise. As a result, only a few compounds such as Tc-hexamethylpropyleneamineoxime,F-FDG, the oldest but still considered as a gold standard In-oxine, and, yes, evenGa-citrate in some countries, have remained in routine clinical practice. Nonetheless, the interest of scientists and physicians to improve the approaches to imaging and to the management of infection is noteworthy. These approaches have paved the way for the development of numerous, innovative radiopharmaceuticals to label autologous WBCs ex vivo or even those that could be injected directly to image infection or inflammation without direct involvement of WBCs. In this review, we briefly describe these agents with their pros and cons and place them together for future reference.

An update on radiotracer development for molecular imaging of bacterial infections

“…This review is an update of our earlier review published in 2013 [14], as well as other thematic reviews [12,[15][16][17][18][19][20][21].…”

Localization Mechanisms of Radiopharmaceuticals

“…The lactoferrin bind with indium more firmly than oxine and free oxine (8-hydroxyquinoline) leave the cell environment. Scintigraphy using 111 In-oxine (8-hydroxyquinoline) with labeled leukocytes (WBCs) were the clinically proved agent of choice for detecting infection foci accurately [43,44].…”

“…Glucose-6-phosphate further participate in glycolysis but FDG-6-phosphate cannot metabolized (not being the subsequent substrate) as glycolytic enzyme glucose-6-phosphate isomerase (hexokinase) has strict structural and geometric demands so fluorine substituted; 2-oxy-2-fluoro-D-glucose trapped and accumulate inside cell cytoplasm (metabolic trapping) [44]. Remember that glucose and FDG compete for the same transporter GLUT-1, so higher glucose level may lower the uptake of FDG.…”

The Future of Nuclear Medicine as an Independent Specialty

“…Imaging biomarkers include small molecules, peptides and peptidomimetics, and antibodies and antibody fragments (18)(19)(20)(21). Small molecules-metabolic and cell surface receptor-targeted probes-can successfully improve the management and outcome of patients affected by neurodegenerative (22), cardiovascular (23), inflammatory and infectious diseases (24), and cancer (4,5).…”