New Development in Radio-iodinated Radiopharmaceuticals for SPECT and Radionuclide Therapy: [123I]/[131I] labelled L- and D- Phenylalanine analogues

Matthias Bauwens, John Mertens, Ken Kersemans, Tony Lahoutte, Axel Bossuyt

Research output: Contribution to journalArticle

Abstract

[123/125I]-2-Iodo-L-phenylalanine and [123/125I]-2-Iodo-D-phenylalanine, with the radioiodine atom on the 2 position of the aromatic ring, were evaluated as potential specific tumour tracers for SPECT. The tracers were obtained with an overall radiochemical yield of at least 98% and a purity of > 99 % in one-pot Kit conditions. The tracers were evaluated in vitro using R1M rhabdomyosarcoma cells as cancer cell model. The initial uptake of [125I]-2-Iodo-D-phenylalanine is slower than that of the L analogue but up from 20 minutes the uptake as function of time is the same. The uptake of the D analogue is proven to occur by the same LAT transport system used by L amino acid and to be satiable resulting in a Km value of 32µM comparable with the L analogue. Although both compounds showed an apparent accumulation over 24 hours no incorporation 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 (DPI) . [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 occurred through the kidneys to the bladder resulting in low tracer activity in the abdomen. The activity in the brain was also low. Specific tumour uptake was confirmed using [99mTc]-PP and by displacement with L-Phe. In rats both tracers showed a high in vivo stability up to 2 hours p.i., almost no free radioiodide and no other labelled metabolites were observed. The characteristics of the biodistribution make [123I]-2-Iodo-L- and D-phenylalanine promising tumour specific tracers for SPECT. The long-term retention of the activity in the tumours coupled to a profound clearance from blood and tissue make these tracers candidate for radionuclide therapy with 131I.
Original languageEnglish
Pages (from-to)223-232
Number of pages10
JournalTrends in Radiopharmaceuticals ISTR 2005(IAEA), Volume 2: 223-32.
Volume2
Publication statusPublished - 2005

Keywords

  • 123I
  • Tumour
  • D-Amino acid

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