Page 119 - Cellular Imaging in Regenerative Medicine, Cancer and Osteoarthritis

Stabilized Sarabesin-3 for prostate imaging
28, 29]. The large amount of unlabeled compound might hamper formation and detection of radiometabolites, so caution is advised when comparing the results of the low and high peptide amounts. However, even when using a high amount of peptide a clear effect of PA was still observed.
The metabolic susceptibility of peptides can be influenced by a multitude of characteristics. Next to the peptide structure, also charge and configuration can play a role. The most well-known approach to protect peptides against degradation is modify the peptide, e.g. by stabilizing peptide bonds. It was found that specific changes of the C-terminal structure of peptide gastrin releasing peptide analogues resulted in receptor antagonists with improved potency and stability [38]. Previously it has been reported that charge, peptide chain length, choice of linker, etc can all, have large effects on metabolic stability and pharmacokinetics of GRP ligands [39, 40].
Concerning the biodistribution studies, stabilization of [111In]SB3 by inhibition of NEP, resulted in higher tumor uptake. Next to higher tumor uptake, high uptake of the radiotracer was also observed in the pancreas. Even though the radiopeptide uptake in the pancreas increased when [111In]SB3 was co- administered with PA, the tumor to pancreas ratio remained unaffected. Nevertheless, this high uptake in the pancreas should be kept in mind when the radiotracer would be used for radio-guided surgery of lesions close to the pancreas. In this case the surgeon should carefully evaluate whether the signal measured by a gamma detection probe and/or a handheld gamma camera is derived from tumor lesions or neighboring healthy tissue. However, as can be seen from the biodistribution data, radioactivity washout from the pancreas was relatively fast, while tumor radioactivity uptake declined at a lower rate. This was also observed in previously published studies [11, 41- 43]. So, determining the time window with optimal tumor/pancreas ratio is required for optimal pre-operative and intra-operative tumor detection. In this respect, the uptake in the kidneys and the bladder due to renal excretion of the radiotracer should also be taken into account.
An interesting next step would be to modify the peptide to create a molecule that can serve both as radioactivity- and fluorescence-carrier. Even though radio-guided surgery is profitable, it has limitations. So, the use of radiotracers
117
5