Facile stereospecific synthesis and biological evaluation of (S)- and (R)-2-amino-2-methyl-4-[123I]iodo-3-(E)-butenoic acid for brain tumor imaging with single photon emission computerized tomography.
Both enantiomers of 2-amino-2-methyl-4-iodo-3-(E)-butenoic acid (IVAIB, 5) were radioiodoinated in 65-72% yield. (S)-IVAIB entered 9L gliosarcoma cells primarily via A-type transport in vitro with higher uptake than (R)-IVAIB. Biodistribution studies in rats with 9L gliosarcoma brain tumors demonstrated higher tumor to brain ratios with (S)-IVAIB (75:1 at 1 h) than (R)-IVAIB (7.7:1). In this model, (S)-IVAIB is superior to (R)-IVAIB and is a promising radiotracer for brain tumor imaging.
Yu
Weiping
W
mgoodma@emory.edu.
McConathy
Jonathan
J
Olson
Jeffrey
J
Camp
Vernon M
VM
Goodman
Mark M
MM
D000409:Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000000981:diagnostic imaging*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging*; D005229:Fatty Acids, Monounsaturated / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018316:Gliosarcoma / Q000000981:diagnostic imaging*; D007457:Iodine Radioisotopes; D008297:Male; D009368:Neoplasm Transplantation; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
C527731:2-amino-2-methyl-4-iodo-3-butenoic acid; D000596:Amino Acids; D005229:Fatty Acids, Monounsaturated; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D000409:Alanine