In order to improve tracers for amino acid transport studies with SPET we have radioiodinated methylated tyrosines and compared their brain uptake and in vivo deiodination in mice. O-methylation not only leads to a higher lipophilicity and hence significantly higher brain uptake with a maximum of 5% dose/g for 3-[123I]iodo-O-methyl-L-alpha-methyltyrosine (OMIMT) but also significantly prevents in vivo deiodination. High n.c.a. radioiodination yields (> or = 80%) are obtained for the activated aromatic compounds L-tyrosine and L-alpha-methyltyrosine using Iodo-gen iin a heterogeneous aqueous system. Direct n.c.a. radioiodination of the less-activated O-methyl analogues has been achieved in reasonable yields (60%) with Iodo-gen in homogeneous TFA solutions containing about 10% of water.