l-Methyl-methionine-indocyanine green derivative 02

Excerpt

A variety of ¹¹C- and ¹⁸F-labeled amino acids have been studied for potential use in positron emission tomography (PET) oncology (1, 2). Most brain tumors show an increased uptake of amino acids as compared with normal brain tissues (3). These amino acids are composed of naturally occurring amino acids, such as l-[¹¹C]leucine, S-[¹¹C]methyl-l-methionine ([¹¹C]MET), and l-[¹¹C]tyrosine, and non-natural amino acids, such as [¹¹C]aminoisobutyric acid, [¹¹C]1-aminocyclopentane-1-carboxylic acid, and [¹¹C]1-aminocyclobutane-1-carboxylic acid. ¹²³I-Labeled amino acids are also used in oncological imaging (1, 4, 5). Some 20 amino acid transporter systems have been identified (1). Most amino acids are taken up by tumor cells through an energy-independent l-type amino acid transporter system, a Na-dependent transporter system A, or a Na⁺-dependent system B⁰ (6). They are retained in tumor cells due to their metabolic activities, including incorporation into proteins, which are higher than most normal cells (1). Malignant transformation increases the use of amino acids for energy, protein synthesis, and cell division. Tumor cells have been found to have overexpressed transporter systems (7). l-[¹¹C]MET, [¹⁸F]fluorotyrosine, l-[¹¹C]leucine, and [¹⁸F]fluoro-α-methyl tyrosine have been widely used in the detection of tumors (2, 6) but are not approved by the United States Food and Drug Administration. These agents are moved into cells by various amino acid transporters and are incorporated into proteins. The fraction of radiolabeled amino acid that is incorporated into protein is usually small compared to the total amount taken up into the cell, except for leucine, which is quantitatively incorporated into proteins. These natural amino acid imaging agents are based on amino acid transport and protein incorporation.

[¹¹C]MET has been widely used in the detection of brain, head and neck, lung, and breast cancers, as well as lymphomas (2) [PubMed]. [¹¹C]MET can cross the blood–brain barrier, and while it is incorporated mainly into proteins, [¹¹C]MET is also incorporated into lipid, RNA, and DNA. [¹¹C]MET PET imaging is more sensitive to radiotherapy compared to [¹⁸F]FDG and is useful for monitoring treatment of cancer. Among the various optical imaging agents, only indocyanine green (ICG), with NIR fluorescence absorption at 780 nm and emission at 820 nm, is approved by the United States Food and Drug Administration for clinical applications in angiography, blood flow evaluation, and liver function assessment (8-11). It is also under evaluation in several clinical trials for other applications, such as optical imaging and mapping of both the lymphatic vessels and lymph nodes in cancer patients for surgical dissection of tumor cells, as well as endoscopic imaging of the pancreas and colon. ICG derivative 02 (ICG-Der-02) contains one carboxyl functional group for covalent conjugation to the amino group of biomolecules. ICG-Der-02 is a hydrophilic dye. Mahounga et al. (12) evaluated Met-ICG-Der-02 for in vivo NIR optical imaging in tumor-bearing mice.