Synthesis and characterization of rhenium and technetium-99m labeled insulin

Chitra Sundararajan; Travis R. Besanger; Renee Labiris; Katharina J. Guenther; Thomas Strack; Robert Garafalo; Thomas T. Kawabata; Deborah Finco-Kent; Jon Zubieta; John W. Babich; John F. Valliant

doi:10.1021/jm100096c

Synthesis and characterization of rhenium and technetium-99m labeled insulin

Chitra Sundararajan, Travis R. Besanger, Renee Labiris, Katharina J. Guenther, Thomas Strack, Robert Garafalo, Thomas T. Kawabata, Deborah Finco-Kent, Jon Zubieta, John W. Babich, John F. Valliant

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

A ^99mTc-labeled insulin analogue was synthesized through a direct labeling method in which the [^99mTc(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 ^99mTc-labeled product was confirmed by HPLC. Displacement of ¹²⁵I-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 ^99mTc-insulin derivative as a tracer for studying insulin biochemistry in vivo

Original language	English (US)
Pages (from-to)	2612-2621
Number of pages	10
Journal	Journal of Medicinal Chemistry
Volume	53
Issue number	6
DOIs	https://doi.org/10.1021/jm100096c
State	Published - Mar 25 2010

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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title = "Synthesis and characterization of rhenium and technetium-99m labeled insulin",

abstract = "A 99mTc-labeled insulin analogue was synthesized through a direct labeling method in which the [99mTc(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 99mTc-labeled product was confirmed by HPLC. Displacement of 125I-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 99mTc-insulin derivative as a tracer for studying insulin biochemistry in vivo",

author = "Chitra Sundararajan and Besanger, {Travis R.} and Renee Labiris and Guenther, {Katharina J.} and Thomas Strack and Robert Garafalo and Kawabata, {Thomas T.} and Deborah Finco-Kent and Jon Zubieta and Babich, {John W.} and Valliant, {John F.}",

year = "2010",

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doi = "10.1021/jm100096c",

language = "English (US)",

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AU - Sundararajan, Chitra

AU - Besanger, Travis R.

AU - Labiris, Renee

AU - Guenther, Katharina J.

AU - Strack, Thomas

AU - Garafalo, Robert

AU - Kawabata, Thomas T.

AU - Finco-Kent, Deborah

AU - Zubieta, Jon

AU - Babich, John W.

AU - Valliant, John F.

PY - 2010/3/25

Y1 - 2010/3/25

N2 - A 99mTc-labeled insulin analogue was synthesized through a direct labeling method in which the [99mTc(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 99mTc-labeled product was confirmed by HPLC. Displacement of 125I-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 99mTc-insulin derivative as a tracer for studying insulin biochemistry in vivo

AB - A 99mTc-labeled insulin analogue was synthesized through a direct labeling method in which the [99mTc(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 99mTc-labeled product was confirmed by HPLC. Displacement of 125I-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 99mTc-insulin derivative as a tracer for studying insulin biochemistry in vivo

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Synthesis and characterization of rhenium and technetium-99m labeled insulin

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