Euromedim 2006 :1st European Conference on Molecular Imaging Technology

In vivo PET evaluation in tumour bearing rats of [18F]-2-fluoromethyl-L-phenylalanine as a new potential tracer for molecular imaging of brain and extra-cranial tumours in humans with PET.In vivo PET evaluation in tumour bearing rats of [18F]-2-fluoromethyl-L-phenylalanine as a new potential tracer for molecular imaging of brain and extra-cranial tumours in humans with PET.

12 May 2006, 09:30

15m

Palais du Pharo, Marseille

oral S9_S10 Molecular Imaging Molecular Imaging

Speaker

Prof. John Mertens (BEFY, Vrije Universiteit Brussel)

Description

The Na+-independent L-type LAT amino acid transport system 1 for neutral and lipophilic amino acids has been shown to be increased in tumour tissue relative to normal tissue, and the LAT system has been regarded as a key-point for the development of new amino acid based tumour tracers for molecular imaging. We have proven in vitro and in vivo that the new compound 2-I-L-phenylalanine is taken up in R1M and in several types of human cancer cells by LAT for the major part. This radio-iodinated amino acid show a very high tumour selectivity when compared to the work horse for oncology PET, [18F]-FDG, which is taken up considerably in brain and inflammatory tissue. Therefore we developed a new fluorinated phenylalanine analogue, [18F]-2-fluoromethyl-L-phenylalanine ([18F]-2-Me-L-Phe), considering that the special volume of FCH3 is comparable with that of the I atom in 2-I-L- phenylalanine and which could be prepared with the ease of [18F]-FDG to allow clinical routine. The substrate molecule for radio labeling 2-Bromomethyl-L-phenylalaine was custom prepared by radical bromination of Me-L-Phe. [18F]- for bromo exchange is performed within 5 minutes in conditions comparable to FDG synthesis with a radiochemical yield of at least 85%. After deprotection (15 minutes) the [18F]-2-fluoromethyl-L- phenylalanine is recovered n.c.a. with a high purity by means of semi-prep HPLC in a solution which after make-up and sterilization is ready for injection. 3.7 – 10 MBq were injected into R1M rat rhabdomyosarcoma bearing tumours with a volume ranging from 1cm3 to 2.7 cm3. Imaging was performed with a human Siemens Acsel PET camera from 5 to 45 minutes p.i.. Quantification of activity uptake occurred by conventional algorithms. The tumour (shoulder or flank) / background (contra lateral shoulder or flank) and tumour / blood ratios obtained from PET acquisition were at least 3. This was confirmed by measurement of the activity in organs and tissue of interest after dissection. A small tumour implanted near a kidney could be well visualized completely separated from this kidney. Moreover in all tumours the “living” tumour cells can clearly be differentiated from necrotic tissue. This proves that [18F] 2-fluoromethyl-L-phenylalanine has a great potential as a new tracer for specific tumour diagnosis with PET.