Synthesis and characterization of rhenium and technetium-99m labeled insulin.
A (99m)Tc-labeled insulin analogue was synthesized through a direct labeling method in which the [(99m)Tc(CO)(3)](+) core was combined with a protected insulin derivative (9) bearing a M(I) chelate linked to the first amino acid of the B-chain (B1). Regioselective labeling was achieved by careful control over the pH and the reaction time. Following a TFA-anisole mediated deprotection step (decay-corrected yield of 30 +/- 11%, n = 4), the identity of the final (99m)Tc-labeled product was confirmed by HPLC. Displacement of (125)I-insulin from the insulin receptor (IR) by the Re analogue 6 was similar to that of native insulin (17.8 nM vs 11.7 nM, respectively). The extent of autophosphorylation and Akt activation, as indicated by production of phospho-Akt (pAkt), showed no statistical difference between 6 and native insulin in both assays. These results support the use of the reported (99m)Tc-insulin derivative as a tracer for studying insulin biochemistry in vivo.
Departments of Chemistry and Medical Physics & Applied Radiation Sciences, McMaster University, Hamilton, Ontario L8S 4M1, Canada.
Chitra
C
Sundararajan
Travis R
TR
Besanger
Renee
R
Labiris
Katharina J
KJ
Guenther
Thomas
T
Strack
Robert
R
Garafalo
Thomas T
TT
Kawabata
Deborah
D
Finco-Kent
Jon
J
Zubieta
John W
JW
Babich
John F
JF
Valliant
D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007328:Insulin / Q000737:chemistry*; D008956:Models, Chemical; D008969:Molecular Sequence Data; D015394:Molecular Structure; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D012211:Rhenium / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013667:Technetium / Q000737:chemistry*
D007328:Insulin; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D012211:Rhenium; D013667:Technetium