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

Abstract

The Na +-independent l-type LAT1 amino acid transport system for large and neutral amino acids has been shown to be expressed higher in tumour tissue relative to normal tissue and has been regarded as a key point for the development of new amino acid based tumour tracers for molecular imaging. We developed a new fluorinated phenylalanine analogue, 2-[ 18F]fluoromethyl- l-phenylalanine, considering that the spatial volume of FCH 3 is comparable with that of the iodine atom in 2-I- l-phenylalanine, of which we have proven that it is taken up excellently in tumours by the LAT1 system. The substrate molecule for radiolabeling, Boc-2-bromomethyl- l-phenylalanine- tButylester, was prepared by radical bromination of Boc-2-methyl- l-phenylalanine- tButylester. [ 18F −] for bromine exchange is performed within 3 min in conditions comparable to the [ 18F]FDG synthesis with a radiochemical yield of at least 85%. After deprotection and semi-preparative HPLC purification, the 2-[ 18F]fluoromethyl- l-phenylalanine is recovered n.c.a. (57%) with a high purity and 3.7 MBq were injected into R1M rhabdomyosarcoma tumour-bearing rats. Imaging was performed with a human PET camera from 5 to 45 min p.i. The tumour/background and tumour/blood ratios obtained from PET acquisition were at least 2.5. DUR values for the tumours were at least about 5. Furthermore, a small tumour implanted near a kidney could be well visualized completely separated from this kidney. Moreover in all tumours the “active” tumour tissue can clearly be differentiated from less active tumour tissue. This proves that 2-[ 18F]fluoromethyl- l-phenylalanine has a great potential as a new tracer for specific tumour diagnosis with PET.