Uptake of [ N -methyl - 11 C]α-methylaminoisobutyric acid in untreated head and neck cancer studied by PET

Abstract

Amino acid transport system A is expressed strongly in neoplastic cells. [ N-methyl-(11)C]alpha-Methylaminoisobutyric acid ((11)C-MeAIB) is a recently developed tracer for PET studies on system A amino acid transport. (11)C-MeAIB is a metabolically stable amino acid analogue which is transported from plasma into the tissue by system A. This study evaluated the kinetics of (11)C-MeAIB uptake from plasma into tumour tissue and normal tissues in 13 patients with untreated head and neck cancer. (11)C-MeAIB uptake in tumour was compared with histological grade and proliferative activity. Tracer uptake was quantitated by calculating the standardised uptake values (SUVs) and the kinetic influx constants ( K(i)) using graphical analysis. All tumours accumulated (11)C-MeAIB and were visualised clearly. In the graphical analysis, linear plots were achieved; the mean K(i) value of tumour was 0.056+/-0.026 min(-1), and the mean SUV was 6.1+/-2.7. A close correlation between graphically obtained K(i) and semi-quantitative SUV in tumours was found ( r=0.887, P=0.00005). We could not demonstrate a correlation between the uptake of (11)C-MeAIB and the grade of malignancy or the proliferative index, as assessed using Ki-67 immunohistochemical assay. Head and neck cancer can be effectively imaged with (11)C-MeAIB PET. (11)C-MeAIB showed active and rapid transport into tumour tissue and salivary glands. Further studies on the applicability of (11)C-MeAIB PET for radiation treatment planning in the head and neck region and the regulation of system A amino acid transport under different metabolic states are warranted.

Relationship between [ 14 C]MeAIB uptake and amino acid transporter family gene expression levels or proliferative activity in a pilot study in human carcinoma cells: Comparison with [ 3 H]methionine uptake

“…A study in cultured human erythroleukemic (K562) cells using radiolabeled [ 14 C]MeAIB also gave the same result [34]. Given all of data, it is thought that system A is the principal [ 11 C]MeAIB transport pathway in in vivo human PET studies [19,20], although no human PET study has been conducted in the presence of amino acid transport inhibitors. In our study using four different types of human carcinoma cells we have shown that system A contributes more than 70% to [ 14 C]MeAIB uptake.…”

“…Compared with [ 11 C]MET, [ 11 C]MeAIB is metabolically stable [17] and it has been studied both pre-clinically and clinically. For example, [ 11 C]MeAIB has been shown to be useful in the measurement of amino acid uptake into skeletal muscle and in the diagnosis of malignant lymphoma and head and neck cancers [18][19][20]. In our institute, [ 11 C]MeAIB PET has proven useful in the diagnosis of chest diseases, especially in the differential diagnosis between sarcoidosis and metastasis [21].…”

Non-natural amino acids for tumor imaging using positron emission tomography and single photon emission computed tomography

“…The high degree of regulation of system A transport by factors such as amino acid availability [51,[63][64][65]190] has been proposed as a major source of this observed variability. In a more recent study using [ 11 C]MeAIB in 13 patients with known head and neck cancer, increased uptake was observed in all known lesions [191]. However, the uptake of [ 11 C]MeAIB was somewhat variable (SUV 2.4 to 11.5) and did not correlate with tumor proliferation rate as measured by Ki-67 staining or tumor grade.…”

Placental Phenotypes of Intrauterine Growth

“…Development of such novel tests is the exciting prospect that can now be glimpsed. Possibilities include measurement of transporter activity in the fragments of MVM plasma membranes, which are shed into maternal blood during every pregnancy (52) or the use of positron emission tomography with suitable tracer substrates to image placental transporter activity in utero: a suitable substrate for System A ([N-methyl-11C]alpha-methylaminoisobutyric acid) is now available (53). These specific diagnostic tests are essential prerequisites for developing the currently nonexistent in utero therapies for fetal growth anomalies, which are the ultimate goal.…”