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Abstract: Angiogenesis is a multi-step process regulated by pro- and anti-angiogenic factors. Inhibition of angiogenesis is a potential anti cancer treatment strategy that is now investigated clinically. In addition, advances in the understanding of the angiogenic process have led to the development of new angiogenesis therapies for ischemic heart disease. Currently, researchers search for objective measures that indicate pharmacological responses to pro- and anti-angiogenic drugs and therefore, there is a great interest in techniques to visualize angiogenesis noninvasively. As CD13 is selectively expressed in angiogenic blood vessels, it can serve as a target for molecular imaging tracers to noninvasively visualize angiogenic processes in animal models and patients. Here, an overview on the currently used CD13 targeted molecular imaging probes for noninvasive visualization of angiogenesis is given. [Copyright &y& Elsevier]

Purpose: Due to the restricted expression of αβ in tumours, αβ is considered a suitable receptor for tumour targeting. In this study the αβ-binding characteristics of Ga-labelled monomeric, dimeric and tetrameric RGD peptides were determined and compared with their In-labelled counterparts. Methods: A monomeric (E-c(RGDfK)), a dimeric (E-[c(RGDfK)]) and a tetrameric (E{E[c(RGDfK)]}) RGD peptide were synthesised, conjugated with DOTA and radiolabelled with Ga. In vitro αβ-binding characteristics were determined in a competitive binding assay. In vivo αβ-targeting characteristics of the compounds were assessed in mice with subcutaneously growing SK-RC-52 xenografts. In addition, microPET images were acquired using a microPET/CT scanner. Results: The IC values for the Ga(III)-labelled DOTA-E-c(RGDfK), DOTA-E-[c(RGDfK)] and DOTA-E{E[c(RGDfK)]} were 23.9 ± 1.22, 8.99 ± 1.20 and 1.74 ± 1.18 nM, respectively, and were similar to those of the In(III)-labelled mono-, di- and tetrameric RGD peptides (26.6 ± 1.15, 3.34 ± 1.16 and 1.80 ± 1.37 nM, respectively). At 2 h post-injection, tumour uptake of the Ga-labelled mono-, di- and tetrameric RGD peptides (3.30 ± 0.30, 5.24 ± 0.27 and 7.11 ± 0.67%ID/g, respectively) was comparable to that of their In-labelled counterparts (2.70 ± 0.29, 5.61 ± 0.85 and 7.32 ± 2.45%ID/g, respectively). PET scans were in line with the biodistribution data. On all PET scans, the tumour could be clearly visualised. Conclusion: The integrin affinity and the tumour uptake followed the order of DOTA-tetramer > DOTA-dimer > DOTA-monomer. The Ga-labelled tetrameric RGD peptide has excellent characteristics for imaging of αβ expression with PET. [ABSTRACT FROM AUTHOR]