RT Journal Article
SR Electronic
T1 <sup>76</sup>Br and <sup>123</sup>I radiolabeled amino acids for tumor imaging using PET and SPECT
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1183
OP 1183
VO 55
IS supplement 1
A1 Burkemper, Jennifer
A1 Huang, Chaofeng
A1 Sultan, Debbie
A1 Yuan, Liya
A1 Klaas, Amanda
A1 Mebrahtu, Efrem
A1 Rich, Keith
A1 McConathy, Jonathan
A1 Lapi, Suzanne
YR 2014
UL http://jnm.snmjournals.org/content/55/supplement_1/1183.abstract
AB 1183 Objectives Amino acid transport is upregulated in many tumors cells due to increased demand for nutrients, making radiolabeled amino acids useful for tumor imaging and potentially for therapeutic applications. While there are many types of amino acid transporters relevant to tumor imaging, system A is of particular interest due to its unidirectional influx of amino acids into the cell under physiological conditions. The purpose of this work was to exploit this transport by synthesizing the novel 76Br-labeled (BrVAIB) and N-methylated/123I-labeled MeIVAIB) analogues of the previously reported (S)-2-amino-2-methyl-4-[123I]-iodo-3-(E)-butenoic acid (IVAIB-Yu,J. Med. Chem., 2007) and compare the properties of these compounds in the mouse DBT glioma model. Methods The desired vinyl-trimethyl tin precursor was synthesized in four steps from enantiopure N-boc-α-methyl-L-serine. N-methylation required extra steps due to protecting group manipulation. Radioiodination reactions were carried out with [123I]NaI, H2O2 and HCl. Bromine labeling was executed using peracetic acid and [76Br] NH4Br in water. Compounds were deprotected, isolated using ion-retardation resin in series with C-18 cartridges and analyzed using chiral high performance liquid chromatography (HPLC). Results Both (S)-[76Br]BrVAIB and (S)-[123I]IVAIB were synthesized in good yields (50-60 % isolated) and purities &gt; 99%. Biodistribution studies demonstrated maximal tumor uptake of [123I]IVAIB at 2.7 + 0.6 %ID/gram 30 min post injection comparative to [76Br]BrVAIB with 2.8 + 0.65 %ID/gram at 2 hr. However, IVAIB revealed higher tumor to normal tissues ratios than BrVAIB. Thyroid uptake was lower than tumor and most tissues, indicating that the compound did not undergo significant de-iodination in vivo. Biological and imaging studies with [123I]IMeVAIB are ongoing. Conclusions (S)-[76Br]BrVAIB can be prepared in high radiochemical yield and demonstrates good uptake in DBT tumors.