This work describes the synthesis and the
tumor affinity testing of no-carrier-added (n.c.a.) p-[(124)I]iodo-L-phenyalanine ([(124)I]IPA) and n.c.a. p-[(131)I]iodo-l-phenyalanine ([(131)I]IPA) as
radiopharmaceuticals for imaging
brain tumors with PET and for radionuclid-based
therapy, respectively. Parameters for labeling were optimized with regard to the amount of precursor, temperature and time. Thereafter, n.c.a. [(124)I]IPA and n.c.a. [(131)I]IPA were investigated in rat F98
glioma and in primary human A1207 and HOM-T3868
glioblastoma cells in vitro, followed by an in vivo evaluation in CD1 nu/nu mice engrafted with human
glioblastoma. No-carrier-added [(124)I]IPA and n.c.a. [(131)I]IPA were obtained in 90+/-6% radiochemical yield and >99% radiochemical purity by iododestannylation of N-Boc-4-(tri-n-butylstannyl)-L-phenylalanine methylester in the presence of
chloramine-T, followed by hydrolysis of the protecting groups. The total synthesis time, including the HPLC separation and pharmacological formulation, was less than 60 min and compatible with a clinical routine production. Both
amino acid tracers accumulated intensively in rat and in human
glioma cells. The radioactivity incorporation in
tumor cells following a 15-min incubation at 37 degrees C/pH 7.4 varied from 25% to 42% of the total loaded activity per 10(6)
tumor cells (296-540 cpm/1000 cells). Inhibition experiments confirmed that n.c.a. [(124)I]IPA and n.c.a. [(131)I]IPA were taken up into
tumor by the
sodium-independent L- and ASC-type transporters. Biodistribution and whole-body imaging by a
gamma-camera and a PET scanner demonstrated a high targeting level and a prolonged retention of n.c.a. [(124)I]IPA and n.c.a. [(131)I]IPA within the xenotransplanted human
glioblastoma and a primarily renal excretion. However, an accurate delineation of the
tumors in mice was not possible by our imaging systems. Radioactivity accumulation in the thyroid and in the stomach as a secondary indication of deiodination was less than 1% of the injected dose at 24h p.i., confirming the high in vivo stability of the
radiopharmaceuticals. In conclusion, n.c.a. [(124)I]IPA and n.c.a. [(131)I]IPA are new promising
radiopharmaceuticals, which can now be prepared in high radiochemical yields and high purity for widespread clinical applications. The specific and high-level targeting of n.c.a. [(124)I]IPA and n.c.a. [(131)I]IPA to
glioma cells in vitro and to
glioblastoma engrafts in vivo encourages further in vivo validations to ascertain their clinical potential as agent for imaging and quantitation of
gliomas with PET, and for radionuclid-based
therapy, respectively.