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Pilot Study of a Novel 18F-labeled FSHR Probe for Tumor Imaging

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Abstract

Purpose

Follicle-stimulating hormone receptor (FSHR) is overexpressed in primary and metastatic tumor. Molecular imaging of FSHR is beneficial for prognosis and therapy of cancer. FSHβ(33–53) (YTRDLVYKDPARPKIQKTCTF), denoted as FSH1, is a FSHR antagonist. In the present study, maleimide-NOTA conjugate of FSH1 (NOTA-MAL-FSH1) was designed and labeled with [18F] aluminum fluoride. The resulting tracer, 18F-Al-NOTA-MAL-FSH1, was preliminarily evaluated in PET imaging of FSHR-positive tumor.

Procedures

NOTA-MAL-FSH1 was synthesized and radiolabeled with Al18F complex. The tumor-targeting potential and pharmacokinetic profile of the 18F-labeled compound were evaluated in vitro and in vivo using a PC3 human prostate tumor model.

Results

18F-Al-NOTA-MAL-FSH1 can be efficiently produced within 30 min with a non-decay-corrected yield of 48.6 ± 2.1 % and a radiochemical purity of more than 95 %. The specific activity was at least 30 GBq/μmol. The radiotracer was stable in phosphate-buffered saline and human serum for at least 2 h. The IC50 values of displacement 18F-Al-NOTA-MAL-FSH1 with FSH1 were 252 ± 1.12 nM. The PC3 human prostate tumor xenografts were clearly visible with high contrast after injection of 18F-Al-NOTA-MAL-FSH1 via microPET. At 30, 60 and 120 min postinjection, the tumor uptakes were 2.98 ± 0.29 % injected dose (ID)/g, 2.53 ± 0.20 %ID/g and 1.36 ± 0.12 %ID/g, respectively. Dynamic PET scanning showed that tumor uptake reached a plateau by about 6 min. Heart peaked earlier and then cleared quickly. Biodistribution studies confirmed that the normal organs except kidney uptakes were all below 1 %ID/g at 1 h p.i. The tumor-to-blood and tumor-to-muscle ratio at 10 min, 0.5, 1, and 2 h after injection were 1.64 ± 0.36, 2.97 ± 0.40, 9.31 ± 1.06, and 13.59 ± 2.33 and 7.05 ± 1.10, 10.10 ± 1.48, 16.17 ± 3.29, and 30.88 ± 4.67, respectively. The tracer was excreted mainly through the renal system, as evidenced by high levels of radioactivity in the kidneys. FSHR-binding specificity was also demonstrated by reduced tumor uptake of 18F-Al-NOTA-MAL-FSH1 after coinjection with an excess of unlabeled FSH1 peptide.

Conclusion

NOTA-MAL-FSH1 could be labeled rapidly and efficiently with 18F using one step method. Favorable preclinical data suggest that 18F-Al-NOTA-MAL-FSH1 may be a suitable radiotracer for the non-invasive visualization of FSHR positive tumor in vivo.

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Acknowledgments

This work was partially supported by National Natural Science Foundation (81171399 and 81101077), CSC Foundation (2011832173), National Significant New Drugs Creation Program (2012ZX09505-001-001), Jiangsu Province Science and Technology Foundation (BE2012622, BK2011166 and BL2012031), Health Ministry of Jiangsu Province Fund (RC2011095 and H201028), public service platform for science and technology infrastructure construction project of Jiangsu Province (BM2012066), and University of Wisconsin-Madison Department of Medical Physics and Department of Radiology (Radiology R&D Award 1105-002).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, 214063, China

    Yuping Xu, Donghui Pan, Lizhen Wang, Fei Chen, Runlin Yang, Shineng Luo & Min Yang

  2. Nanjing Medical University, Nanjing, Jiangsu, 210029, China

    Chen Zhu & Qing Xu

  3. Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, 53705, USA

    Yongjun Yan

Authors
  1. Yuping Xu
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  2. Donghui Pan
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  3. Chen Zhu
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  4. Qing Xu
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  5. Lizhen Wang
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  6. Fei Chen
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  7. Runlin Yang
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  8. Shineng Luo
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  9. Min Yang
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  10. Yongjun Yan
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Corresponding authors

Correspondence to Min Yang or Yongjun Yan.

Additional information

Donghui Pan equally contributes to the work.

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Xu, Y., Pan, D., Zhu, C. et al. Pilot Study of a Novel 18F-labeled FSHR Probe for Tumor Imaging. Mol Imaging Biol 16, 578–585 (2014). https://doi.org/10.1007/s11307-013-0712-1

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  • DOI: https://doi.org/10.1007/s11307-013-0712-1

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