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

Abstract

3-[ 123 I]Iodo-L-a-methyl tyrosine ( 123 I-IMT) is used for diagnosis and monitoring of brain tumours by means of singlephoton emission tomography. As recently shown, 123 I-IMT is predominantly mediated into rat C6 glioma cells by sodiumindependent system L for large neutral amino acids. Until now, 123 I-IMT transport in non-neoplastic glial cells has not been examined. Therefore, the aim of this study was to examine the cellular pathways and precise transport kinetics of 123 I-IMT uptake into astrocytes of neonatal rats. In particular sodiumindependent 123 I-IMT transport into neonatal astrocytes was compared with sodium-independent 123 I-IMT uptake into neoplastic rat C6 glioma cells.Competitive inhibition experiments showed that 123 I-IMT is exclusively transported via sodium-independent system L into the neonatal astrocytes (92%). Kinetic analysis of sodium-independent 123 I-IMT uptake into neonatal astrocytes and into C6 glioma cells revealed apparent Michaelis constants K M 13.9^0.5 mM and K M 33.9^4.1 mM, respectively, which are in the same range of K M values as those recently determined for amino acid transport into neoplastic and non-neoplastic glial cells. Indeed, the K M values in the micromolar range correspond to the expression of the LAT-1 subunit of system L both in the neonatal astrocytes and in C6 glioma cells. However, sodium-independent maximum transport velocities (V max ) differed significantly between neonatal astrocytes and C6 glioma cells (11.1^0.3 and 39.9^3.3 nmol/mg protein/10 min, respectively).

Amino Acid Transporters and Glutamine Metabolism in Breast Cancer

“…Amino acid transporters can be also used for single-photon emission computed tomography (SPECT) imaging of tumors. 3-[ 123 I] Iodo-α-methyl- l -tyrosine (IMT) is an artificial amino acid that is transported via SLC7A5 [ 94 ], as well as a suitable metabolic tracer for SPECT in extracranial tumors including breast cancer [ 95 ]. With IMT SPECT, primary and metastatic breast cancer and regression of tumor after radiotherapy were all detectable and concordant with the clinical assessment results [ 95 ].…”

Systemic Endoradiotherapy with Carrier-Added 4-[131I]Iodo-L-Phenylalanine: Clinical Proof-of-Principle in Refractory Glioma

“…LAT1, therefore, constitutes an attractive target to mediate molecular therapy. Indeed, radiolabelled amino acid derivatives substrate to the LAT1 transporter, such as 11 C-labelled methionine ( 11 C-MET), [ 123 I]iodo-α-methyltyrosine ( 123 I-IMT) and [ 18 F]fluoroethyltyrosine ( 18 F-FET) [12][13][14][15], are established in clinical PET and single-photon emission computed tomography (SPECT) imaging of glioma. While efficiently targeting glioma cells in vivo, a retention in tumour tissue for less than 90 min [16], or a chemical structure unsuitable for radiohalogenation, prevent them to be used as scaffolds for therapeutic iodine-131 labelling.…”

L-Tyrosine availability affects basal and stimulated catecholamine indices in prefrontal cortex and striatum of the rat

“…TH-mediated vs. non-enzymatic mechanisms are often distinguished through administration of a TH-inhibitor, typically α-methyltyrosine or one of its analogues (Nagatsu et al, 1964). As a synthetic LNAA however, α-methyltyrosine also competes with L-TYR for binding to LAT-1, the main LNAA membrane transporter (Kopka et al., 2001). LAT-1, like other LNAA transporters from the L-family is an obligatory 1:1 heteroexchanger; for every LNAA molecule carried in one direction across a membrane, another LNAA molecule must be transported in the opposite direction (del Amo et al, 2008;Uchino et al, 2002).…”