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18F-Fluorosulfate for PET Imaging of the Sodium-Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo.
J Nucl Med 2017; 58(1):156-161JN

Abstract

Anion transport by the human sodium-iodide symporter (hNIS) is an established target for molecular imaging and radionuclide therapy. Current radiotracers for PET of hNIS expression are limited to 124I- and 18F-BF4- We sought new 18F-labeled hNIS substrates offering higher specific activity, higher affinity, and simpler radiochemical synthesis than 18F-BF4-

METHODS:

The ability of a range of anions, some containing fluorine, to block 99mTcO4- uptake in hNIS-expressing cells was measured. SO3F- emerged as a promising candidate. 18F-SO3F- was synthesized by reaction of 18F- with SO3-pyridine complex in MeCN and purified using alumina and quaternary methyl ammonium solid-phase extraction cartridges. Chemical and radiochemical purity and serum stability were determined by radiochromatography. Radiotracer uptake and efflux in hNIS-transduced HCT116-C19 cells and the hNIS-negative parent cell line were evaluated in vitro in the presence and absence of a known competitive inhibitor (NaClO4). PET/CT imaging and ex vivo biodistribution measurement were conducted on BALB/c mice, with and without NaClO4 inhibition.

RESULTS

Fluorosulfate was identified as a potent inhibitor of 99mTcO4- uptake via hNIS in vitro (half-maximal inhibitory concentration, 0.55-0.56 μM (in comparison with 0.29-4.5 μM for BF4-, 0.07 μM for TcO4-, and 2.7-4.7 μM for I-). Radiolabeling to produce 18F-SO3F- was simple and afforded high radiochemical purity suitable for biologic evaluation (radiochemical purity > 95%, decay-corrected radiochemical yield = 31.6%, specific activity ≥ 48.5 GBq/μmol). Specific, blockable hNIS-mediated uptake in HCT116-C19 cells was observed in vitro, and PET/CT imaging of normal mice showed uptake in thyroid, salivary glands (percentage injected dose/g at 30 min, 563 ± 140 and 32 ± 9, respectively), and stomach (percentage injected dose/g at 90 min, 68 ± 21).

CONCLUSION

Fluorosulfate is a high-affinity hNIS substrate. 18F-SO3F- is easily synthesized in high yield and very high specific activity and is a promising candidate for preclinical and clinical PET imaging of hNIS expression and thyroid-related disease; it is the first example of in vivo PET imaging with a tracer containing an S-18F bond.

Authors+Show Affiliations

Division of Imaging Sciences and Biomedical Engineering, St. Thomas' Hospital, King's College London, London, United Kingdom; and.Division of Imaging Sciences and Biomedical Engineering, St. Thomas' Hospital, King's College London, London, United Kingdom; and.Division of Imaging Sciences and Biomedical Engineering, St. Thomas' Hospital, King's College London, London, United Kingdom; and.GE Healthcare, Amersham, United Kingdom.GE Healthcare, Amersham, United Kingdom.Division of Imaging Sciences and Biomedical Engineering, St. Thomas' Hospital, King's College London, London, United Kingdom; and.Division of Imaging Sciences and Biomedical Engineering, St. Thomas' Hospital, King's College London, London, United Kingdom; and.Division of Imaging Sciences and Biomedical Engineering, St. Thomas' Hospital, King's College London, London, United Kingdom; and philip.blower@kcl.ac.uk.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27539841

Citation

Khoshnevisan, Alex, et al. "18F-Fluorosulfate for PET Imaging of the Sodium-Iodide Symporter: Synthesis and Biologic Evaluation in Vitro and in Vivo." Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine, vol. 58, no. 1, 2017, pp. 156-161.
Khoshnevisan A, Chuamsaamarkkee K, Boudjemeline M, et al. 18F-Fluorosulfate for PET Imaging of the Sodium-Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo. J Nucl Med. 2017;58(1):156-161.
Khoshnevisan, A., Chuamsaamarkkee, K., Boudjemeline, M., Jackson, A., Smith, G. E., Gee, A. D., ... Blower, P. J. (2017). 18F-Fluorosulfate for PET Imaging of the Sodium-Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo. Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine, 58(1), pp. 156-161. doi:10.2967/jnumed.116.177519.
Khoshnevisan A, et al. 18F-Fluorosulfate for PET Imaging of the Sodium-Iodide Symporter: Synthesis and Biologic Evaluation in Vitro and in Vivo. J Nucl Med. 2017;58(1):156-161. PubMed PMID: 27539841.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 18F-Fluorosulfate for PET Imaging of the Sodium-Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo. AU - Khoshnevisan,Alex, AU - Chuamsaamarkkee,Krisanat, AU - Boudjemeline,Mehdi, AU - Jackson,Alex, AU - Smith,Gareth E, AU - Gee,Antony D, AU - Fruhwirth,Gilbert O, AU - Blower,Philip J, Y1 - 2016/08/18/ PY - 2016/05/16/received PY - 2016/07/11/accepted PY - 2016/8/20/pubmed PY - 2017/5/2/medline PY - 2016/8/20/entrez KW - 18F KW - PET KW - fluorosulfate KW - human sodium/iodide symporter (SC5A5) KW - thyroid SP - 156 EP - 161 JF - Journal of nuclear medicine : official publication, Society of Nuclear Medicine JO - J. Nucl. Med. VL - 58 IS - 1 N2 - : Anion transport by the human sodium-iodide symporter (hNIS) is an established target for molecular imaging and radionuclide therapy. Current radiotracers for PET of hNIS expression are limited to 124I- and 18F-BF4- We sought new 18F-labeled hNIS substrates offering higher specific activity, higher affinity, and simpler radiochemical synthesis than 18F-BF4- METHODS: The ability of a range of anions, some containing fluorine, to block 99mTcO4- uptake in hNIS-expressing cells was measured. SO3F- emerged as a promising candidate. 18F-SO3F- was synthesized by reaction of 18F- with SO3-pyridine complex in MeCN and purified using alumina and quaternary methyl ammonium solid-phase extraction cartridges. Chemical and radiochemical purity and serum stability were determined by radiochromatography. Radiotracer uptake and efflux in hNIS-transduced HCT116-C19 cells and the hNIS-negative parent cell line were evaluated in vitro in the presence and absence of a known competitive inhibitor (NaClO4). PET/CT imaging and ex vivo biodistribution measurement were conducted on BALB/c mice, with and without NaClO4 inhibition. RESULTS: Fluorosulfate was identified as a potent inhibitor of 99mTcO4- uptake via hNIS in vitro (half-maximal inhibitory concentration, 0.55-0.56 μM (in comparison with 0.29-4.5 μM for BF4-, 0.07 μM for TcO4-, and 2.7-4.7 μM for I-). Radiolabeling to produce 18F-SO3F- was simple and afforded high radiochemical purity suitable for biologic evaluation (radiochemical purity > 95%, decay-corrected radiochemical yield = 31.6%, specific activity ≥ 48.5 GBq/μmol). Specific, blockable hNIS-mediated uptake in HCT116-C19 cells was observed in vitro, and PET/CT imaging of normal mice showed uptake in thyroid, salivary glands (percentage injected dose/g at 30 min, 563 ± 140 and 32 ± 9, respectively), and stomach (percentage injected dose/g at 90 min, 68 ± 21). CONCLUSION: Fluorosulfate is a high-affinity hNIS substrate. 18F-SO3F- is easily synthesized in high yield and very high specific activity and is a promising candidate for preclinical and clinical PET imaging of hNIS expression and thyroid-related disease; it is the first example of in vivo PET imaging with a tracer containing an S-18F bond. SN - 1535-5667 UR - https://www.unboundmedicine.com/medline/citation/27539841/18F_Fluorosulfate_for_PET_Imaging_of_the_Sodium_Iodide_Symporter:_Synthesis_and_Biologic_Evaluation_In_Vitro_and_In_Vivo_ L2 - http://jnm.snmjournals.org/cgi/pmidlookup?view=long&pmid=27539841 DB - PRIME DP - Unbound Medicine ER -