Skip to main content
Log in

Comparison of [11C]Choline ([11C]CHO) and [18F]Bombesin (BAY 86-4367) as Imaging Probes for Prostate Cancer in a PC-3 Prostate Cancer Xenograft Model

  • Research Article
  • Published:
Molecular Imaging and Biology Aims and scope Submit manuscript

Abstract

Purpose

Carbon-11- and fluorine-18-labeled choline derivatives are commonly used in prostate cancer imaging in the clinical setting for staging and re-staging of prostate cancer. Due to a limited detection rate of established positron emission tomography (PET) tracers, there is a clinical need for innovative tumor-specific PET compounds addressing new imaging targets. The aim of this study was to compare the properties of [18F]Bombesin (BAY 86-4367) as an innovative biomarker for prostate cancer imaging targeting the gastrin-releasing peptide receptor and [11C]Choline ([11C]CHO) in a human prostate tumor mouse xenograft model by small animal PET/X-ray computed tomography (CT).

Procedures

We carried out a dual-tracer small animal PET/CT study comparing [18F]Bombesin and [11C]CHO. The androgen-independent human prostate tumor cell line PC-3 was implanted subcutaneously in the flanks of nu/nu NMRI mice (n = 10) (PET/CT measurements of two [11C]Choline mice could not be analyzed due to technical reasons). [18F]Bombesin and [11C]CHO PET/CT imaging was performed about 3–4 weeks after the implantation of PC-3 cells on two separate days. After the intravenous tail vein injection of 14 MBq [18F]Bombesin and 37 MBq [11C]CHO, respectively, a dynamic study over 60 min was acquired in list mode using an Inveon animal PET/CT scanner (Siemens Medical Solutions). The sequence of [18F]Bombesin and [11C]CHO was randomized. Image analysis was performed using summed images as well as dynamic data. To calculate static and dynamic tumor-to-muscle (T/M), tumor-to-blood (T/B), liver-to-blood (L/B), and kidney-to-blood (K/B) ratios, 4 × 4 × 4 mm3 volumes of interest (VOIs) of tumor, muscle (thigh), liver, kidney, and blood derived from transversal slices were used.

Results

The mean T/M ratio of [18F]Bombesin and [11C]CHO was 6.54 ± 2.49 and 1.35 ± 0.30, respectively. The mean T/B ratio was 1.83 ± 0.79 for [18F]Bombesin and 0.55 ± 0.10 for [11C]CHO. The T/M ratio as well as the T/B ratio for [18F]Bombesin were significantly higher compared to those for [11C]CHO (p < 0.001, respectively). Kidney and liver uptake was statistically significantly lower for [18F]Bombesin (K/B 3.41 ± 0.81, L/B 1.99 ± 0.38) compared to [11C]CHO [K/B 7.91 ± 1.85 (p < 0.001), L/B 6.27 ± 1.99 (p < 0.001)]. The magnitudes of the time course of T/M and T/B ratios (T/M and T/Bdyn ratios) were statistically significantly different (showing a higher uptake of [18F]Bombesin compared to [11C]CHO); additionally, also the change of the T/M and T/B ratios over time was significantly different between both tracers in the dynamic analysis (p < 0.001, respectively). Furthermore, there was a statistically significantly different change of the K/B and L/B ratios over time between the two tracers in the dynamic analysis (p = 0.026 and p < 0.001, respectively).

Conclusions

[18F]Bombesin (BAY 86-4367) visually and semi-quantitatively outperforms [11C]CHO in the PC-3 prostate cancer xenograft model. [18F]Bombesin tumor uptake was significantly higher compared to [11C]CHO. [18F]Bombesin showed better imaging properties compared to the clinically utilized [11C]CHO due to a higher tumor uptake as well as a lower liver and kidney uptake.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Price DT, Coleman RE, Liao RP et al (2002) Comparison of [18 F]fluorocholine and [18 F]fluorodeoxyglucose for positron emission tomography of androgen dependent and androgen independent prostate cancer. J Urol 168:273–280

    Article  PubMed  Google Scholar 

  2. Zheng QH, Gardner TA, Raikwar S et al (2004) [11C]Choline as a PET biomarker for assessment of prostate cancer tumor models. Bioorg Med Chem 12:2887–2893

    Article  CAS  PubMed  Google Scholar 

  3. Ramirez de Molina A, Penalva V, Lucas L, Lacal JC (2002) Regulation of choline kinase activity by Ras proteins involves Ral-GDS and PI3K. Oncogene 21:937–946

    Article  CAS  PubMed  Google Scholar 

  4. Ramirez de Molina A, Rodriguez-Gonzalez A, Gutierrez R et al (2002) Overexpression of choline kinase is a frequent feature in human tumor-derived cell lines and in lung, prostate, and colorectal human cancers. Biochem Biophys Res Commun 296:580–583

    Article  CAS  PubMed  Google Scholar 

  5. Hara T, Bansal A, DeGrado TR (2006) Choline transporter as a novel target for molecular imaging of cancer. Mol Imaging 5:498–509

    PubMed  Google Scholar 

  6. Katz-Brull R, Degani H (1996) Kinetics of choline transport and phosphorylation in human breast cancer cells; NMR application of the zero trans method. Anticancer Res 16:1375–1380

    CAS  PubMed  Google Scholar 

  7. Schwarzenboeck SM, Gertz J, Souvatzoglou M et al (2015) Comparison of [(11)C]choline ([(11)C]CHO) and S(+)-beta-methyl-[(11)C]choline ([(11)C]SMC) as imaging probes for prostate cancer in a PC-3 prostate cancer xenograft model. Mol Imaging Biol 17:248–256

    Article  Google Scholar 

  8. Markwalder R, Reubi JC (1999) Gastrin-releasing peptide receptors in the human prostate: relation to neoplastic transformation. Cancer Res 59:1152–1159

    CAS  PubMed  Google Scholar 

  9. Honer M, Mu L, Stellfeld T et al (2011) 18F-labeled bombesin analog for specific and effective targeting of prostate tumors expressing gastrin-releasing peptide receptors. J Nucl Med 52:270–278

    Article  CAS  PubMed  Google Scholar 

  10. Bergmann R, Ruffani A, Graham B et al (2013) Synthesis and radiopharmacological evaluation of (6)(4)Cu-labeled bombesin analogs featuring a bis(2-pyridylmethyl)-1,4,7-triazacyclononane chelator. Eur J Med Chem 70:434–446

    Article  CAS  PubMed  Google Scholar 

  11. Mansi R, Wang X, Forrer F et al (2009) Evaluation of a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-conjugated bombesin-based radioantagonist for the labeling with single-photon emission computed tomography, positron emission tomography, and therapeutic radionuclides. Clin Cancer Res 15:5240–5249

    Article  CAS  PubMed  Google Scholar 

  12. Nanda PK, Pandey U, Bottenus BN et al (2012) Bombesin analogues for gastrin-releasing peptide receptor imaging. Nucl Med Biol 39:461–471

    Article  CAS  PubMed  Google Scholar 

  13. Nock B, Nikolopoulou A, Chiotellis E et al (2003) [99mTc]Demobesin 1, a novel potent bombesin analogue for GRP receptor-targeted tumour imaging. Eur J Nucl Med Mol Imaging 30:247–258

    Article  CAS  PubMed  Google Scholar 

  14. Pan D, Xu YP, Yang RH et al (2014) A new (68)Ga-labeled BBN peptide with a hydrophilic linker for GRPR-targeted tumor imaging. Amino Acids 46:1481–1489

    Article  CAS  PubMed  Google Scholar 

  15. Pan D, Yan Y, Yang R et al (2014) PET imaging of prostate tumors with 18F-Al-NOTA-MATBBN. Contrast Media Mol Imaging 9:342–348

    Article  CAS  PubMed  Google Scholar 

  16. Richter S, Wuest M, Krieger SS et al (2013) Synthesis and radiopharmacological evaluation of a high-affinity and metabolically stabilized 18F-labeled bombesin analogue for molecular imaging of gastrin-releasing peptide receptor-expressing prostate cancer. Nucl Med Biol 40:1025–1034

    Article  CAS  PubMed  Google Scholar 

  17. Varasteh Z, Aberg O, Velikyan I et al (2013) In vitro and in vivo evaluation of a (18)F-labeled high affinity NOTA conjugated bombesin antagonist as a PET ligand for GRPR-targeted tumor imaging. PLoS One 8:e81932

    Article  PubMed  PubMed Central  Google Scholar 

  18. Yang M, Gao H, Zhou Y et al (2011) F-labeled GRPR agonists and antagonists: a comparative study in prostate cancer imaging. Theranostics 1:220–229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zhang H, Abiraj K, Thorek DL et al (2012) Evolution of bombesin conjugates for targeted PET imaging of tumors. PLoS One 7:e44046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sah BR, Burger IA, Schibli R et al (2015) Dosimetry and first clinical evaluation of the new 18F-radiolabeled bombesin analogue BAY 864367 in patients with prostate cancer. J Nucl Med 56:372–378

    Article  CAS  PubMed  Google Scholar 

  21. Schroeder RP, van Weerden WM, Krenning EP et al (2011) Gastrin-releasing peptide receptor-based targeting using bombesin analogues is superior to metabolism-based targeting using choline for in vivo imaging of human prostate cancer xenografts. Eur J Nucl Med Mol Imaging 38:1257–1266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Cescato R, Maina T, Nock B et al (2008) Bombesin receptor antagonists may be preferable to agonists for tumor targeting. J Nucl Med 49:318–326

    Article  CAS  PubMed  Google Scholar 

  23. Abd-Elgaliel WR, Gallazzi F, Garrison JC et al (2008) Design, synthesis, and biological evaluation of an antagonist-bombesin analogue as targeting vector. Bioconjug Chem 19:2040–2048

    Article  CAS  PubMed  Google Scholar 

  24. Hara T, Yuasa M (1999) Automated synthesis of [11C]choline, a positron-emitting tracer for tumor imaging. Appl Radiat Isot 50:531–533

    Article  CAS  PubMed  Google Scholar 

  25. Henriksen G, Herz M, Hauser A et al (2004) Synthesis and preclinical evaluation of the choline transport tracer deshydroxy-[18F]fluorocholine ([18F]dOC). Nucl Med Biol 31:851–858

    Article  CAS  PubMed  Google Scholar 

  26. Bao Q, Newport D, Chen M et al (2009) Performance evaluation of the Inveon dedicated PET preclinical tomograph based on the NEMA NU-4 standards. J Nucl Med 50:401–408

    Article  PubMed  PubMed Central  Google Scholar 

  27. Mu L, Honer M, Becaud J et al (2010) In vitro and in vivo characterization of novel 18F-labeled bombesin analogues for targeting GRPR-positive tumors. Bioconjug Chem 21:1864–1871

    Article  CAS  PubMed  Google Scholar 

  28. Zhang X, Cai W, Cao F et al (2006) 18F-labeled bombesin analogs for targeting GRP receptor-expressing prostate cancer. J Nucl Med 47:492–501

    CAS  PubMed  Google Scholar 

  29. Benesova M, Schafer M, Bauder-Wust U et al (2015) Preclinical evaluation of a tailor-made DOTA-conjugated PSMA inhibitor with optimized linker moiety for imaging and endoradiotherapy of prostate cancer. J Nucl Med 56:914–920

    Article  CAS  PubMed  Google Scholar 

  30. Lesche R, Kettschau G, Gromov AV et al (2014) Preclinical evaluation of BAY 1075553, a novel (18)F-labelled inhibitor of prostate-specific membrane antigen for PET imaging of prostate cancer. Eur J Nucl Med Mol Imaging 41:89–101

    Article  CAS  PubMed  Google Scholar 

  31. Weineisen M, Schottelius M, Simecek J et al (2015) 68Ga- and 177Lu-labeled PSMA I&T: optimization of a PSMA targeted theranostic concept and first proof of concept human studies. J Nucl Med 56:1169–1176

    Article  CAS  PubMed  Google Scholar 

  32. Weineisen M, Simecek J, Schottelius M et al (2014) Synthesis and preclinical evaluation of DOTAGA-conjugated PSMA ligands for functional imaging and endoradiotherapy of prostate cancer. EJNMMI Res 4:63

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors thank Sybille Reder, Elisabeth Aiwanger, Annette Frank, and Rosel Oos for their great technical support.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sarah Marie Schwarzenböck.

Ethics declarations

Conflict of Interest.

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schwarzenböck, S.M., Schmeja, P., Kurth, J. et al. Comparison of [11C]Choline ([11C]CHO) and [18F]Bombesin (BAY 86-4367) as Imaging Probes for Prostate Cancer in a PC-3 Prostate Cancer Xenograft Model. Mol Imaging Biol 18, 393–401 (2016). https://doi.org/10.1007/s11307-015-0901-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11307-015-0901-1

Key words

Navigation