NEW DEVELOPMENT IN RADIOIODINATEDRADIOPHARMACEUTICALS FOR SPECT ANDRADIONUCLIDE THERAPY: 123I/131I LABELLEDL- AND D-PHENYLALANINE ANALOGUES

摘要

[123/125I]-2-Iodo-L-phenylalanine and [123/125I]-2-Iodo-D-phenylalanine, with the radioiodine atom in the 2 position of the aromatic ring, were evaluated as potentialspecific tumour tracers for SPECT. The tracers were obtained with an overall radio radio-chemical yield of at least 98% and a purity of >99% in one pot kit conditions. Thetracers were evaluated in vitro using R1M rhabdomyosarcoma cells as the cancer cellmodel. The initial uptake of [125I]-2-Iodo-D-phenylalanine is slower than that of the L--analogue but from 20 min the uptake as a function of time is the same. The uptake of theD- analogue is proven to occur by the same LAT transport system used by L amino acidand to be satiable, resulting in a Km value of 32μM comparable with the L- analogue.Although both compounds showed an apparent accumulation over 24 h, no incorpora incorpora-tion was noticed. In vivo, the biodistribution of [ 123/125I]-2-Iodo-L- and D-phenylalanine-in R1M rhabdomyosarcoma bearing rats was measured by dynamic planar imaging.[99mTc]-PP planar imaging was performed to correct for blood pool activity. [123I]-2--Iodo-D-phenylalanine showed a DUR value of 2.9 at 30 min p.I., while for [123I]-2-Iodo--L-phenylalanine, the DUR value reached 3.2. Blood clearance of the tracers occurredthrough the kidneys to the bladder, resulting in low tracer activity in the abdomen. Theactivity in the brain was also low. Specific tumour uptake was confirmed using [99mTc]- PP and by displacement with L-phenylalanine. In rats, both tracers showed a high in vivostability up to 2 h p.I., almost no free radioiodide and no other labelled metabolites wereobserved. The characteristics of the biodistribution make [123I]-2-Iodo-L- and D-phenylalanine promising tumour specific tracers for SPECT. The long term retention of theactivity in the tumours coupled to a profound clearance from blood and tissue makethese tracers candidates for radionuclide therapy with 131I.