TY - JOUR
T1 - Synthesis of a [18F]-labeled ceritinib analogue for positron emission tomography of anaplastic lymphoma kinase, a receptor tyrosine kinase, in lung cancer
AU - Perera, Sandun
AU - Piwnica-Worms, David
AU - Alauddin, Mian M.
N1 - Funding Information:
This work was supported by the National Institutes of Health through the Washington University-MD Anderson Cancer Center Inter-Institutional Molecular Imaging Center grant (NCI P50 CA94056) (DP-W) and by an MD Anderson Cancer Center Institutional Research Grant (MMA).
Publisher Copyright:
© Copyright 2016 John Wiley & Sons, Ltd.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - Anaplastic lymphoma kinase (ALK), an oncogenic receptor tyrosine kinase, has emerged as a therapeutic target in solid and hematologic tumors. Although several ALK inhibitors have gained recent approval for therapy, non-invasive indicators of target engagement or for use as predictive biomarkers in vivo are lacking. Therefore, we designed and synthesized a radiolabeled analogue of the ALK inhibitor ceritinib, [18F]fluoroethyl-ceritinib ([18F]-FEC), for use with positron emission tomography. We used two methods to synthesize [18F]-FEC. First, [18F]fluoroethyl-tosylate was prepared, coupled with ceritinib, and the product purified to yield [18F]-FEC. Alternatively, a precursor compound was synthesized, directly fluorinated with 18F-fluoride, and purified to yield [18F]-FEC. The first method produced [18F]-FEC with an average decay-corrected yield of 24% (n = 4), specific activity of 1200 mCi/μmol, and >99% purity; synthesis time was 115 min from the end of bombardment. The second method produced [18F]-FEC with an average yield of 7% (n = 4), specific activity of 1500 mCi/μmol, and >99% purity; synthesis time was 65 min from the end of bombardment. The synthesis of a novel 18F-labeled analogue of ceritinib has been achieved in acceptable yields, at high purity, and with high specific activity. The compound is a potential positron emission tomography imaging agent for the detection of ALK-overexpressing solid tumors such as lung cancer. Synthesis of [18F]-fluoroethyl-ceritinib for positron emission tomography is reported. Reaction of [18F]-fluoroethyl-tosylate with ceritinib produced the product in good yield, with high purity and specific activity. The compound is a potential positron emission tomography imaging agent for the detection of anaplastic lymphoma kinase-overexpressing solid tumors such as lung cancer.
AB - Anaplastic lymphoma kinase (ALK), an oncogenic receptor tyrosine kinase, has emerged as a therapeutic target in solid and hematologic tumors. Although several ALK inhibitors have gained recent approval for therapy, non-invasive indicators of target engagement or for use as predictive biomarkers in vivo are lacking. Therefore, we designed and synthesized a radiolabeled analogue of the ALK inhibitor ceritinib, [18F]fluoroethyl-ceritinib ([18F]-FEC), for use with positron emission tomography. We used two methods to synthesize [18F]-FEC. First, [18F]fluoroethyl-tosylate was prepared, coupled with ceritinib, and the product purified to yield [18F]-FEC. Alternatively, a precursor compound was synthesized, directly fluorinated with 18F-fluoride, and purified to yield [18F]-FEC. The first method produced [18F]-FEC with an average decay-corrected yield of 24% (n = 4), specific activity of 1200 mCi/μmol, and >99% purity; synthesis time was 115 min from the end of bombardment. The second method produced [18F]-FEC with an average yield of 7% (n = 4), specific activity of 1500 mCi/μmol, and >99% purity; synthesis time was 65 min from the end of bombardment. The synthesis of a novel 18F-labeled analogue of ceritinib has been achieved in acceptable yields, at high purity, and with high specific activity. The compound is a potential positron emission tomography imaging agent for the detection of ALK-overexpressing solid tumors such as lung cancer. Synthesis of [18F]-fluoroethyl-ceritinib for positron emission tomography is reported. Reaction of [18F]-fluoroethyl-tosylate with ceritinib produced the product in good yield, with high purity and specific activity. The compound is a potential positron emission tomography imaging agent for the detection of anaplastic lymphoma kinase-overexpressing solid tumors such as lung cancer.
KW - F
KW - PET
KW - ceritinib
KW - lung cancer
KW - tyrosine kinase
UR - http://www.scopus.com/inward/record.url?scp=84959453081&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84959453081&partnerID=8YFLogxK
U2 - 10.1002/jlcr.3373
DO - 10.1002/jlcr.3373
M3 - Article
C2 - 26853088
AN - SCOPUS:84959453081
SN - 0362-4803
VL - 59
SP - 103
EP - 108
JO - Journal of Labelled Compounds and Radiopharmaceuticals
JF - Journal of Labelled Compounds and Radiopharmaceuticals
IS - 3
ER -