UittrekselThe LAT1 amino acid transport system, over-expressed in many tumour types, has become an important key in tumour imaging using radiolabeled amino acids. Since some neutral D- enantiomeric amino acids can be taken up through the LAT1 system but not by other amino acid transporters, they have a potential as specific tumour tracers as well as radiotherapeutic agents.
In this thesis, radioiodinated D-tyrosine and D- phenylalanine were evaluated and compared with their L-analogues. It was established that both [123I]-2-I-D-tyrosine and [123I]-2-I-D- phenylalanine were taken up in tumour cells via the LAT1 transporter. We found that Phe analogues are superior to Tyr analogues in vivo in terms of tumour residence time and tumour/background contrast at later time points. [123I]-2-I-D-phenylalanine was found to display a favourable biodistribution and dosimetry in human test subjects, with a lower effective dose compared to [123I]-2-I-L-phenylalanine. Finally, [131I]-2-I-D-phenylalanine, evaluated as a potential therapeutic compound in a R1M tumour bearing mouse model, significantly reduced the tumour growth in the treated animals, without substantial side effects.
In conclusion, [123/131I]-2-I-D-phenylalanine shows the promising properties to become a potential cancer theragnostic.
|Datum Prijs||5 mrt 2009|
|Begeleider||John Mertens (Promotor), Tony Lahoutte (Co-promotor), Christiaan Van Schravendijk (Jury), Hendrik Everaert (Jury), Bart Neyns (Jury), Ilse Smolders (Jury), Marion De Jong (Jury), Filip De Vos (Jury) & Alfons Verbruggen (Jury)|