Integrin alpha(v)beta(3) plays a significant role in
tumor angiogenesis and is a receptor for the
extracellular matrix proteins with the exposed
arginine-
glycine-aspartic (
RGD) tripeptide sequence. These include
vitronectin,
fibronectin,
fibrinogen,
lamin,
collagen, Von Willibrand's factor, osteoponin, and adenovirus particles.
Integrin alpha(v)beta(3) is expressed at low levels on epithelial cells and mature endothelial cells, but it is overexpressed on the activated endothelial cells of
tumor neovasculature and some
tumor cells. The restricted expression of
integrin alpha(v)beta(3) during
tumor growth, invasion, and
metastasis presents an interesting molecular target for both early detection and treatment of rapidly growing solid
tumors. Over the past decade, many radiolabeled linear and
cyclic RGD peptide antagonists have been evaluated as
integrin alpha(v)beta(3)-targeted radiotracers. Significant progress has been made on their use for imaging
integrin alpha(v)beta(3)-positive
tumors by SPECT or PET. Among the radiotracers evaluated in preclinical
tumor-bearing models, [18F]Galacto-RGD (2-[18F]fluoropropanamide c(RGDfK(SAA); SAA = 7-amino-L-glyero-L-galacto-2,6-anhydro-7-deoxyheptanamide) and [
18F]-AH111585 are currently under clinical investigation for visualization of
integrin alpha(v)beta(3) expression in
cancer patients. However, their low
tumor uptake, high cost, and lack of preparative modules for routine radiosynthesis will limit their continued clinical application. Thus, there is a continuing need for more efficient
integrin alpha(v)beta(3)-targeted radiotracers that are readily prepared from a kit formulation without further postlabeling purification. This article will focus on different approaches to maximize the targeting capability of
cyclic RGD peptides and to improve the radiotracer excretion kinetics from noncancerous organs. Improvement of
tumor uptake and
tumor-to-background ratios is important for early detection of
integrin alpha(v)beta(3)-positive
tumors and/or noninvasive monitoring of therapeutic efficacy of antiangiogenic
therapy.