Abstract
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Objectives An approach to open up the possibilities for individualized medicine as the same target molecule will be used for diagnostic monitoring and for target oriented therapy. iRGD is a cyclic peptide containing the key RGD αvβ3 integrin targeting sequence and a cryptic CendR sequence (1),(2),(3).
Methods Here, we compared for the first time iRGD peptides; mono, with pegylation 200C9 and 200C1 as tracers for brain, prostate and melanoma cancers. All three iRGDs were synthesised by SPPS and radiolabelled with 68-Ga under acidic conditions. Tracer biodistribution studies and μPET imaging were carried out in SCID mice bearing respectively brain-, prostate- and melanoma carcinoma. Histopathology for detection of αVβ3 and Neuropilin-1 was performed ex vivo.
Results All peptides were readily labelled with high radiochemical yield and purity. Three hours p.i., the accumulation (%ID/g) of 200C9 increased in all tumours, whereas accumulation of 200C1 was slightly decreasing. 200C9 was also retained longer in blood and kidney and with significant higher tumour to muscle ratios than for 200C1. The PEG position accounted for the differing kinetics. Mono seems to have altogether the most promising kinetics, as it has much lower uptake in the kidneys as both C9 and C1 and increasing tumour to muscle ratios after 3 hours p.i. Nonetheless, μPET with all peptides visualized αvβ3 in all carcinomas.
Conclusions The immunostaining confirmed expression of αvβ3 mainly associated with tumour vasculature, in addition to neuropilin-1 staining on tumour cell surfaces. These preliminary data indicate that all three iRGD peptides allow monitoring of αvβ3 expression by μPET, and confirmed internalisation of tumour tissue neuropilin-1 ex vivo. We are currently labeling mono and 200C9 with 177-Lu for therapy studies.
Research Support (1) Sugahara et.al., 2010 (2) Teesalu et al., 2009 (3) Ye et al., 2011