TY - JOUR
T1 - Folate-PEG-NOTA-Al18F
T2 - A New Folate Based Radiotracer for PET Imaging of Folate Receptor-Positive Tumors
AU - Chen, Qingshou
AU - Meng, Xiangjun
AU - McQuade, Paul
AU - Rubins, Daniel
AU - Lin, Shu An
AU - Zeng, Zhizhen
AU - Haley, Hyking
AU - Miller, Patricia
AU - González Trotter, Dinko
AU - Low, Philip
PY - 2017/12/4
Y1 - 2017/12/4
N2 - The folate receptor (FR) has been established as a promising target for imaging and therapy of cancer (FR-α), inflammation, and autoimmune diseases (FR-β). Several folate based PET radiotracers have been reported in the literature, but an 18F-labeled folate-PET imaging agent with optimal properties for clinical translation is still lacking. In the present study, we report the design and preclinical evaluation of folate-PEG12-NOTA-Al18F (1), a new folate-PET agent with improved potential for clinical applications. Radiochemical synthesis of 1 was achieved via a one-pot labeling process by heating folate-PEG12-NOTA in the presence of in situ prepared Al18F for 15 min at 105 °C, followed by HPLC purification. Specific binding of 1 to FR was evaluated on homogenates of KB (FR-positive) and A549 (FR-deficient) tumor xenografts in the presence and absence of excess folate. In vivo tumor imaging with folate-PEG12-NOTA-Al18F was compared to imaging with 99mTc-EC20 using nu/nu mice bearing either KB or A549 tumor xenografts. Specific accumulation of 1 in tumor and other tissues was assessed by high-resolution micro-PET and ex vivo biodistribution in the presence and absence of excess folate. Radiosynthesis of 1 was accomplished within -35 min, affording pure radiotracer 1 in 8.4 ± 1.3% (decay corrected) radiochemical yield with 100% radiochemical purity after HPLC purification and a specific activity of 35.8 ± 15.3 GBq/mmol. Further in vitro and in vivo examination of 1 demonstrated highly specific FR-mediated uptake in FR+ tumor, with Kd of -0.4 nM (KB), and reduced accumulation in liver. Given its facile preparation and improved properties, the new radiotracer, folate-PEG12-NOTA-Al18F (1), constitutes a promising tool for identification and classification of patients with FR overexpressing cancers.
AB - The folate receptor (FR) has been established as a promising target for imaging and therapy of cancer (FR-α), inflammation, and autoimmune diseases (FR-β). Several folate based PET radiotracers have been reported in the literature, but an 18F-labeled folate-PET imaging agent with optimal properties for clinical translation is still lacking. In the present study, we report the design and preclinical evaluation of folate-PEG12-NOTA-Al18F (1), a new folate-PET agent with improved potential for clinical applications. Radiochemical synthesis of 1 was achieved via a one-pot labeling process by heating folate-PEG12-NOTA in the presence of in situ prepared Al18F for 15 min at 105 °C, followed by HPLC purification. Specific binding of 1 to FR was evaluated on homogenates of KB (FR-positive) and A549 (FR-deficient) tumor xenografts in the presence and absence of excess folate. In vivo tumor imaging with folate-PEG12-NOTA-Al18F was compared to imaging with 99mTc-EC20 using nu/nu mice bearing either KB or A549 tumor xenografts. Specific accumulation of 1 in tumor and other tissues was assessed by high-resolution micro-PET and ex vivo biodistribution in the presence and absence of excess folate. Radiosynthesis of 1 was accomplished within -35 min, affording pure radiotracer 1 in 8.4 ± 1.3% (decay corrected) radiochemical yield with 100% radiochemical purity after HPLC purification and a specific activity of 35.8 ± 15.3 GBq/mmol. Further in vitro and in vivo examination of 1 demonstrated highly specific FR-mediated uptake in FR+ tumor, with Kd of -0.4 nM (KB), and reduced accumulation in liver. Given its facile preparation and improved properties, the new radiotracer, folate-PEG12-NOTA-Al18F (1), constitutes a promising tool for identification and classification of patients with FR overexpressing cancers.
KW - F-PET imaging
KW - AlF-NOTA
KW - cancer imaging
KW - folate conjugate
KW - folate receptor
UR - http://www.scopus.com/inward/record.url?scp=85037648744&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85037648744&partnerID=8YFLogxK
U2 - 10.1021/acs.molpharmaceut.7b00415
DO - 10.1021/acs.molpharmaceut.7b00415
M3 - Article
C2 - 29028357
AN - SCOPUS:85037648744
VL - 14
SP - 4353
EP - 4361
JO - Molecular pharmaceutics
JF - Molecular pharmaceutics
SN - 1543-8384
IS - 12
ER -