An artificial amino acid radiopharmaceutical for single photon emission computed tomographic study of pancreatic amino acid transports123I-3-iodo-alpha-methyl-L-tyrosine

Abstract

123I-3-iodo-alpha-methyl-L-tyrosine (123I-L-AMT) was selected and its characteristics on pancreas accumulation, metabolic selectivity and metabolic stability of 125I-L-AMT were studied. The studies on rat tissue slice as well as mouse biodistribution proved very high accumulation of 125I-labeled L-AMT in the pancreas, which was remarkably inhibited by the active transport inhibitor, ouabain. 125I-L-AMT does not enter into protein synthesis and general amino acid catabolism. Moreover, 125I-L-AMT was very stable against enzymatic deiodination. Thus, the above studies indicated that the 123I-labeled L-AMT was an "artificial amino acid" radiopharmaceutical to be used for the selective measurement of the membrane amino acid transport rate in the pancreas.

Characterization of 3-[125I]iodo-α-methyl-L-tyrosine transport via human L-type amino acid transporter 1

“…125 I]IMT and 3-I-Tyr were prepared using the conventional chloramine-T method, as described elsewhere [1,2]. Synthesis of inactive IMT was performed according to the method of Krummeich et al [13].…”

“…1) was developed as a functional imaging agent for Tyr transport mechanisms in the brain [1] and pancreas [2]. It is a nonmetabolizable artificial amino acid that has also been used clinically for SPECT imaging of tumors [3].…”

Synthesis of 99mTc-EC-AMT as an imaging probe for amino acid transporter systems in breast cancer

“…Our findings were consistent with other reported studies regarding radiolabeled tyrosine analogs. For instance, 11 C/ 14 C-tyrosine [22], 123 I/ 125 I-labeled AMT [13,23], 18 F-labeled tyrosine [24], AMT [5], and fluoroethyltyrosine [25] have been proven to be predominantly transported through the amino acid transporter LAT. Increased expression level of LAT has been observed in various types of tumors [15], therefore, upregulated LAT is a suitable target for tumor imaging.…”

Characterization of 3‐[123I]iodo‐L‐α‐methyl tyrosine transport in astrocytes of neonatal rats

“…123 I‐IMT, like other large neutral amino acids, can permeate the intact blood–brain barrier but is not incorporated into cerebral proteins (Kawai et al 1992; Langen et al. 1997, 2000; Heiss et al 1999).…”

“…1997, 2000; Heiss et al 1999). It is assumed that 123 I‐IMT enters the cells by the transport system for large neutral amino acids (sodium‐independent system L ) (Kawai et al 1992). As previously shown, 123 I‐IMT uptake both in normal brain and in gliomas can be reduced by giving infusions of naturally occurring α‐amino acids (Langen et al.…”