Recent developments in radiolabelled peptides for PET imaging of cancer

From Carbon-11-Labeled Amino Acids to Peptides in Positron Emission Tomography: the Synthesis and Clinical Application

“…Carbon-11 Amino Acid Labeling of [1][2][3][4][5][6][7][8][9][10][11] C]Carboxyl-Function Bucherer-Strecker Synthesis The Strecker reaction, and its modified Bucherer-Strecker hydantoin synthesis, is one of the earliest one-pot and atom economic multi-component reactions for AA synthesis in general. The simplicity of the synthesis-simple mixing of the reagents acetaldehyde, ammonia (or amines) and hydrogen cyanide resulting in an α-aminonitrile adduct and its subsequent hydrolysis-has attracted radiochemists to synthesize [ 11 [29], whereas the second approach employed [ 11 C]CO 2 which reacted with α-lithiated precursor [30].…”

“…The simplicity of the synthesis-simple mixing of the reagents acetaldehyde, ammonia (or amines) and hydrogen cyanide resulting in an α-aminonitrile adduct and its subsequent hydrolysis-has attracted radiochemists to synthesize [ 11 [29], whereas the second approach employed [ 11 C]CO 2 which reacted with α-lithiated precursor [30]. In both cases, subsequent hydrolysis affords the corresponding AA as exemplified by Hayes et al [1-11 C]Aminocyclopentanecarboxylic acid (ACPC) was first obtained by a two-step high temperature reaction of cylcopentanone with […”

“…3a, a vast number of racemic [ 11 C]AAs have been described in literature, namely phenylalanine [26], ornithine and lysine [38], tyrosine [28,30], proline [39] and phenylglycine [26], and achiral glycine [25,26]. The [1][2][3][4][5][6][7][8][9][10][11] C]proline has been reported in 12-18 % RCY with a RCP of 9 95 % in total synthesis time of 45 min [39].…”

“…Due to many favorable properties for molecular imaging, such as advantageous pharmacokinetics and specific tumor targeting characteristics, including the overexpression of peptide receptors on the tumor cells, radiolabeled peptides have an important impact not only in PET imaging of cancer, but also in targeted radionuclide therapy [10]. Peptide-based radiopharmaceuticals have been successfully employed for imaging of somatostatin (SST) and bombesin or cholecystokinin/gastrin receptor overexpressing tumors, all common human cancers [10][11][12][13][14].…”

“…Isotopologue labeling without structural modifications conveniently includes C-11 as a normal constituent in well-characterized molecules of known biological properties [6,[21][22][23]. Currently, there is a great toolbox available for labeling AAs with C-11, which includes viable methods using two major C-11 precursors produced directly by cyclotrons: [ 11 11 C-alkylating agents [23]. The half-life of C-11 is, with the current radiolabeling techniques, long enough to perform multi-step synthesis and biological PET tracer analysis [24].…”