Molecular Imaging and Biology

, Volume 14, Issue 3, pp 376–383 | Cite as

Correlation of the Ga-68-Bombesin Analog Ga-68-BZH3 with Receptors Expression in Gliomas as Measured by Quantitative Dynamic Positron Emission Tomography (dPET) and Gene Arrays

  • Ludwig G. Strauss
  • Dirk Koczan
  • Marcel Seiz
  • Jochen Tuettenberg
  • Kirsten Schmieder
  • Leyun Pan
  • Caixia Cheng
  • Antonia Dimitrakopoulou-Strauss
Research Article

Abstract

Purpose

The kinetics of Ga-68-BZH3, a Ga-68-bombesin analog, was compared to molecular biological data obtained from gene arrays in seven patients with a recurrent glioma. The primary aim of this study was the correlation of receptor expression and tracer kinetics.

Procedures

Dynamic positron emission tomography studies were performed and the data were analyzed by a volume-of-interest technique using a two-tissue compartment model as well as a non-compartment model. Gene array data were obtained from gene array analysis of tumor tissue samples.

Results

The correlation analysis revealed a significant nonlinear correlation of r = 0.89 (p < 0.03) for k1 and BB2 (gastrin-releasing peptide receptor). BB1 and BB3 were not significantly correlated with k1. vb and k3 were not significantly correlated with the expression data of the receptors on the p < 0.05 level.

Conclusions

The parameter k1 is correlated with the expression of BB2 based on gene array data. The quantitative analysis of the Ga-68-BZH3 kinetics can be used to predict the receptor expression of BB2 in gliomas based on k1 of the compartment analysis. However, this study is limited to the expression data on the mRNA level and further studies are needed to assess the correlation of gene expression on the protein level.

Key words

PET Ga-68-bombesin GRPR Neuromedin B Bombesin subtype 3 BB1 BB2 BB3 Gene array Glioma 

References

  1. 1.
    Strauss LG, Conti PS (1991) The applications of PET in clinical oncology. J Nucl Med 32:623–648PubMedGoogle Scholar
  2. 2.
    Strauss LG (1996) Fluorine-18 deoxyglucose and false-positive results: a major problem in the diagnostics of oncological patients. Eur J Nucl Med Mol Imaging 23:1409–1415CrossRefGoogle Scholar
  3. 3.
    Dimitrakopoulou-Strauss A, Strauss LG (2008) The role of 18F-FLT in cancer imaging: does it really reflect proliferation? Eur J Nucl Med Mol Imaging 35:523–526PubMedCrossRefGoogle Scholar
  4. 4.
    Dimitrakopoulou-Strauss A, Georgoulias V, Eisenhut et al (2006) Quantitative assessment of SSTR2 expression in patients with non-small cell lung cancer using [68]Ga-DOTATOC PET and comparison with [18]F-FDG PET. Eur J Nucl Med Mol Imaging 33:823–830PubMedCrossRefGoogle Scholar
  5. 5.
    Koukouraki S, Strauss LG, Georgoulias V et al (2006) Evaluation of the pharmacokinetics of 68Ga-DOTATOC in patients with metastatic neuroendocrine tumors scheduled for 90Y-DOTATOC therapy. Eur J Nucl Med Mol Imaging 33:460–466PubMedCrossRefGoogle Scholar
  6. 6.
    Schuhmacher J, Zhang H, Doll J et al (2005) GRP receptor-targeted PET of a rat pancreas carcinoma xenograft in nude mice with a (68)Ga-labeled Bombesin (6–14) analog. J Nucl Med 46:691–699PubMedGoogle Scholar
  7. 7.
    Reubi JC, Wenger S, Schmuckli-Maurer J, Schaer JC, Gugger M (2002) Bombesin receptor subtypes in human cancers: detection with the universal radioligand (125)I-[D-TYR(6), beta-ALA(11), PHE(13), NLE(14)] bombesin(6–14). Clin Cancer Res 8:1139–1146PubMedGoogle Scholar
  8. 8.
    Pradhan TK, Katsuno T, Taylor JE, Kim SH, Ryan RR, Mantey SA, Donohue PJ, Weber HC, Sainz E, Battey JF, Coy DH, Jensen RT, Pradhan TK, Katsuno T, Taylor JE, Kim SH, Ryan RR, Mantey SA, Donohue PJ, Weber HC, Sainz E, Battey JF, Coy DH, Jensen RT (1998) Identification of a unique ligand which has high affinity for all four bombesin receptor subtypes. Eur J Pharmacol 19(343):275–287CrossRefGoogle Scholar
  9. 9.
    Sharif TR, Luo W, Sharif M (1997) Functional expression of bombesin receptor in most adult and pediatric human glioblastoma cell lines; role in mitogenesis and in stimulating the mitogen-activated protein kinase pathway. Mol Cell Endocrinol 130:119–1130PubMedCrossRefGoogle Scholar
  10. 10.
    Dimitrakopoulou-Strauss A, Seiz M, Tuettenberg J et al (2011) Pharmacokinetic studies of 68Ga-labeled Bombesin 68Ga-BZH3] and 18F-FDG PET in patients with recurrent gliomas and comparison to grading: preliminary results. Clin Nucl Med 36:101–108PubMedCrossRefGoogle Scholar
  11. 11.
    Ohtake T, Kosaka N, Watanabe T, Yokoyama I, Moritan T, Masuo M et al (1991) Noninvasive method to obtain input function for measuring glucose utilization of thoracic and abdominal organs. J Nucl Med 32:1432–438PubMedGoogle Scholar
  12. 12.
    Strauss LG, Dimitrakopoulou-Strauss A, Koczan D et al (2004) 18F-FDG kinetics and gene expression in giant cell tumors. J Nucl Med 45:1528–1535PubMedGoogle Scholar
  13. 13.
    Strauss LG, Koczan D, Klippel S et al (2008) Impact of angiogenesis-related gene expression on the tracer kinetics of 18F-FDG kinetics in colorectal tumors. J Nucl Med 49:1238–1244PubMedCrossRefGoogle Scholar
  14. 14.
    Strauss LG, Pan L, Koczan D et al (2007) Fusion of positron emission tomography [PET] and gene array data: a new approach for the correlative analysis of molecular biological and clinical data. IEEE Transactions On Medical Imaging 26:804–812PubMedCrossRefGoogle Scholar
  15. 15.
    Bodei L, Pepe G, Paganelli G (2010) Peptide receptor radionuclide therapy [PRRT] of neuroendocrine tumors with somatostatin analogues. Eur Rev Med Pharmacol Sci 14:347–351PubMedGoogle Scholar
  16. 16.
    Hohla F, Schally AV (2010) Targeting gastrin releasing peptide receptors: New options for the therapy and diagnosis of cancer. Cell Cycle 9:1738–1741PubMedCrossRefGoogle Scholar
  17. 17.
    Flores DG, Meurer L, Uberti AF et al (2010) Gastrin-releasing peptide receptor content in human glioma and normal brain. Brain Res Bull 82:95–98PubMedCrossRefGoogle Scholar
  18. 18.
    Lockhart DJ, Winzeler EA (2000) Genomics, gene expression and DNA arrays. Nature 405:827–836PubMedCrossRefGoogle Scholar
  19. 19.
    Pascal LE, True LD, Campbell DS, Deutsch EW, Risk M, Coleman IM, Eichner LJ, Nelson PS, Liu AY (2008) Correlation of mRNA and protein levels: cell type-specific gene expression of cluster designation antigens in the prostate. BMC Genomics 23(9):246CrossRefGoogle Scholar
  20. 20.
    Tan CS, Salim A, Ploner A, Lehtiö J, Chia KS, Pawitan Y (2009) Correlating gene and protein expression data using Correlated Factor Analysis. BMC Bioinforma 10:272CrossRefGoogle Scholar
  21. 21.
    de Oliveira MS, Cechim G, Braganhol E et al (2009) Anti-proliferative effect of the gastrin-release peptide receptor antagonist RC-3095 plus temozolomide in experimental glioblastoma models. J Neurooncol 93:191–201PubMedCrossRefGoogle Scholar
  22. 22.
    Seiz M, Dimitrakopoulou-Strauss A, Schubert GA et al (2008) Differentiation between malignant transformation and tumour recurrence by [68]Ga-Bombesin and [18]F-FDG-PET, in patients with low grade gliomas. Hell J Nucl Med 11:149–152PubMedGoogle Scholar
  23. 23.
    Kang JH, Ishola TA, Baregamian N et al (2007) Bombesin induces angiogenesis and neuroblastoma growth. Cancer Lett 253:273–281PubMedCrossRefGoogle Scholar
  24. 24.
    Liu X, Carlisle DL, Swick MC, Gaither-Davis A, Grandis JR, Siegfried JM (2007) Gastrin-releasing peptide activates Akt through the epidermal growth factor receptor pathway and abrogates the effect of gefitinib. Exp Cell Res 15(313):1361–1372CrossRefGoogle Scholar
  25. 25.
    Scopinaro F, De Vincentis G, Corazziari E et al (2004) Detection of colon cancer with 99mTc-labeled bombesin derivative [99mTc-leu13-BN1]. Cancer Biother Radiopharm 19:245–252PubMedCrossRefGoogle Scholar
  26. 26.
    Scopinaro F, De Vincentis G, Varvarigou AD et al (2003) 99mTc-bombesin detects prostate cancer and invasion of pelvic lymph nodes. Eur J Nucl Med Mol Imaging 30:1378–1382PubMedCrossRefGoogle Scholar

Copyright information

© Academy of Molecular Imaging and Society for Molecular Imaging 2011

Authors and Affiliations

  • Ludwig G. Strauss
    • 1
  • Dirk Koczan
    • 2
  • Marcel Seiz
    • 3
  • Jochen Tuettenberg
    • 4
  • Kirsten Schmieder
    • 5
  • Leyun Pan
    • 1
  • Caixia Cheng
    • 1
  • Antonia Dimitrakopoulou-Strauss
    • 1
  1. 1.Medical PET Group—Biological Imaging [E060-1], CCU Nuclear MedicineGerman Cancer Research CenterHeidelbergGermany
  2. 2.Institute of ImmunologyUniversity of RostockRostockGermany
  3. 3.Clinical Department of NeurosurgeryMedical University InnsbruckInnsbruckAustria
  4. 4.Department of NeurosurgeryKlinikum Idar-Oberstein GmbHIdar-ObersteinGermany
  5. 5.Department of NeurosurgeryUniversity of Heidelberg, University Medical Center MannheimMannheimGermany

Personalised recommendations