Abstract
Purpose
We explored the imaging of bombesin receptors and evaluated the clinical use of [99mTc]Demobesin 4 ([99mTc]DB4) in prostate cancer patients.
Procedures
[99mTc]DB4 was prepared according to Good Manufacturing Practice. Patients with prostate cancer underwent serial planar and SPECT imaging up to 3 h after administration. Blood and urine samples were taken to assess pharmacokinetics.
Results
[99mTc]DB4 is safe and clears rapidly from the bloodstream via the kidneys resulting in low background activity. The tracer binds strongly to the gastrin-releasing peptide receptor (GRPR) in vivo as indicated by the high uptake in the pancreas seen in all patients. In patients who had undergone hormone therapy, [99mTc]DB4 did not efficiently image metastatic prostate cancer. In contrast, in newly diagnosed patients local disease was visualised.
Conclusions
The GRPR is an unsuitable target for imaging refractory prostate cancer but may be useful in untreated disease. [99mTc]DB4 is a promising radiopharmaceutical which merits further exploration in this specific group of patients.
Similar content being viewed by others
References
Picchio M, Piert M (2013) Prostate cancer imaging. Eur J Nucl Med Mol Imaging 40(Suppl 1):S1–S4
Outwater EK, Montilla-Soler JL (2013) Imaging of prostate carcinoma. Cancer Control 20:161–176
Murphy G, Haider M, Ghai S, Sreeharsha B (2013) The expanding role of MRI in prostate cancer. AJR Am J Roentgenol 201:1229–1238
Geijer H, Breimer LH (2013) Somatostatin receptor PET/CT in neuroendocrine tumours: update on systematic review and meta-analysis. Eur J Nucl Med Mol Imaging 40:1770–1780
Gugger M, Reubi JC (1999) Gastrin-releasing peptide receptors in non-neoplastic and neoplastic human breast. Am J Pathol 155:2067–2076
Markwalder R, Reubi JC (1999) Gastrin-releasing peptide receptors in the human prostate: relation to neoplastic transformation. Cancer Res 59:1152–1159
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
Reubi JC, Korner M, Waser B et al (2004) High expression of peptide receptors as a novel target in gastrointestinal stromal tumours. Eur J Nucl Med Mol Imaging 31:803–810
Cornelio DB, Meurer L, Roesler R, Schwartsmann G (2007) Gastrin-releasing peptide receptor expression in cervical cancer. Oncology 73:340–345
Jensen RT, Battey JF, Spindel ER, Benya RV (2008) International Union of Pharmacology. LXVIII. Mammalian bombesin receptors: nomenclature, distribution, pharmacology, signaling, and functions in normal and disease states. Pharmacol Rev 60:1–42
Hoffman TJ, Sicckman GL, Volkert WA (1995) Targeting small cell lung cancer using iodinated peptide analogs. J Label Compd Radiopharm 37:321–323
Van de Wiele C, Dumont F, Vanden Broecke R et al (2000) Technetium-99 m RP527, a GRP analogue for visualisation of GRP receptor-expressing malignancies: a feasibility study. Eur J Nucl Med 27:1694–1699
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 19:245–252
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 30:1378–1382
Scopinaro F, Varvarigou A, Ussof W et al (2002) Breast cancer takes up 99mTc bombesin. A preliminary report. Tumori 88:S25–S28
Bodei L, Ferrari M, Nunn A et al (2007) 177Lu-AMBA bombesin analogue in hormone refractory prostate cancer patients: a phase I escalation study with single-cycle administrations. Eur J Nucl Med Mol Imaging 34:S221
Hofmann M, Machtens S, Stief C et al (2004) Feasibility of Ga-68-DOTABOM PET in prostate carcinoma patients. Eur J Nucl Med Mol Imaging 31:S253
Dimitrakopoulou-Strauss A, Hohenberger P, Haberkorn U et al (2007) 68Ga-labeled bombesin studies in patients with gastrointestinal stromal tumors: comparison with 18F-FDG. J Nucl Med 48:1245–1250
Schaefer N, Valencia R, Borkowski S et al (2011) Comparison of BAY 86-4367, a new F-18 labeled bombesin analog, with F-18-ethyl-choline in recurrent and primary prostate cancer patients. J Nucl Med Meet Abstr 52:40
Bergsma H, Kulkarni HR, Mueller D et al (2013) PET/CT imaging with a novel 68Ga-labeled GRP-receptor antagonist, sarabesin 3. First clinical data in patients with prostate and breast cancer. J Nucl Med 54:84P
Schroeder RP, de Visser M, van Weerden WM et al (2009) Androgen-regulated gastrin-releasing peptide receptor expression in androgen-dependent human prostate tumor xenografts. Int J Cancer 126:2826–2834
Van de Wiele C, Dumont F, Dierckx RA et al (2001) Biodistribution and dosimetry of (99 m)Tc-RP527, a gastrin-releasing peptide (GRP) agonist for the visualization of GRP receptor-expressing malignancies. J Nucl Med 42:1722–1727
Nock BA, Maina T (2012) Tetraamine-coupled peptides and resulting 99mTc -radioligands: an effective route for receptor-targeted diagnostic imaging of human tumors. Curr Top Med Chem 12:2655–2667
Nock BA, Nikolopoulou A, Galanis A et al (2005) Potent bombesin-like peptides for GRP-receptor targeting of tumors with 99mTc: a preclinical study. J Med Chem 48:100–110
Commission E (2010) The Rules Governing Medicinal Products in the European Union. Volume 4. EU Guidelines to Good Manufacturing Practice. Annex 13. Investigational Medicinal Products
Decristoforo C, Maina T, Nock B et al (2003) 99mTc -demotate 1: first data in tumour patients-results of a pilot/phase I study. Eur J Nucl Med Mol Imaging 30:1211–1219
Kahkonen E, Jambor I, Kemppainen J et al (2013) In vivo imaging of prostate cancer using [68Ga]-labeled bombesin analog BAY86-7548. Clin Cancer Res 19:5434–5443
Froberg A, Visser M, Maina T et al (2006) Are GRP-receptors present in the human pancreas? J Nucl Med 47:429p
Montet X, Yuan H, Weissleder R, Josephson L (2006) Enzyme-based visualization of receptor-ligand binding in tissues. Lab Investig 86:517–525
Ananias HJ, Yu Z, Hoving HD et al (2013) Application of 99mTechnetium-HYNIC(tricine/TPPTS)-aca-bombesin(7-14) SPECT/CT in prostate cancer patients: a first-in-man study. Nucl Med Biol 40:933–938
Beer M, Montani M, Gerhardt J et al (2012) Profiling gastrin-releasing peptide receptor in prostate tissues: clinical implications and molecular correlates. Prostate 72:318–325
de Visser M, van Weerden WM, de Ridder CM et al (2007) Androgen-dependent expression of the gastrin-releasing peptide receptor in human prostate tumor xenografts. J Nucl Med 48:88–93
Acknowledgments
We gratefully acknowledge the help of Beverley Holman with dosimetry calculations, the financial support of Cancer Research UK and the assistance of the Radiopharmacy Department of St Bartholomews Hospital, London.
Conflict of Interest
The authors declare they have no conflicts of interest
Author information
Authors and Affiliations
Corresponding author
Electronic Supplementary Material
Below is the link to the electronic supplementary material.
ESM 1
(PDF 644 kb)
Rights and permissions
About this article
Cite this article
Mather, S.J., Nock, B.A., Maina, T. et al. GRP Receptor Imaging of Prostate Cancer Using [99mTc]Demobesin 4: a First-in-Man Study. Mol Imaging Biol 16, 888–895 (2014). https://doi.org/10.1007/s11307-014-0754-z
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11307-014-0754-z