Skip to main content
Top
Published in: European Journal of Nuclear Medicine and Molecular Imaging 12/2011

01-12-2011 | Original Article

Quantification of receptor-ligand binding with [18F]fluciclatide in metastatic breast cancer patients

Authors: Giampaolo Tomasi, Laura Kenny, Francesco Mauri, Federico Turkheimer, Eric O. Aboagye

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 12/2011

Login to get access

Abstract

Purpose

The purpose of the study was to estimate the receptor-ligand binding of an arginine-glycine-aspartic acid (RGD) peptide in somatic tumours. To this aim, we employed dynamic positron emission tomography (PET) data obtained from breast cancer patients with metastases, studied with the αvβ3/5 integrin receptor radioligand [18F]fluciclatide.

Methods

First, compartmental modelling and spectral analysis with arterial input function were performed at the region of interest (ROI) level in healthy lung and liver, and in lung and liver metastases; compartmental modelling was also carried out at the pixel level. The selection of the most appropriate indexes for tumour/healthy tissue differentiation and for estimation of specific binding was then assessed.

Results

The two-tissue reversible model emerged as the best according to the Akaike Information Criterion. Spectral analysis confirmed the reversibility of tracer kinetics. Values of kinetic parameters, estimated as mean from parametric maps, correlated well with those computed from ROI analysis. The volume of distribution VT was on average higher in lung metastases than in the healthy lung, but lower in liver metastases than in the healthy liver. In agreement with the expected higher αvβ3/5 expression in pathology, k3 and k3/k4 were both remarkably higher in metastases, which makes them more suitable than VT for tumour/healthy tissue differentiation. The ratio k3/k4, in particular, appeared a reasonable measure of specific binding.

Conclusion

Besides establishing the best quantitative approaches for the analysis of [18F]fluciclatide data, this study indicated that the k3/k4 ratio is a reasonable measure of specific binding, suggesting that this index can be used to estimate αvβ3/5 receptor expression in oncology, although further studies are necessary to validate this hypothesis.
Appendix
Available only for authorised users
Literature
1.
3.
go back to reference Nagengast WB, Lub-de Hooge MN, Oosting SF, den Dunnen WF, Warnders FJ, Brouwers AH et al. VEGF-PET imaging is a noninvasive biomarker showing differential changes in the tumor during sunitinib treatment. Cancer Res 2011;71(1):143–53. doi:10.1158/0008-5472.CAN-10-1088. Nagengast WB, Lub-de Hooge MN, Oosting SF, den Dunnen WF, Warnders FJ, Brouwers AH et al. VEGF-PET imaging is a noninvasive biomarker showing differential changes in the tumor during sunitinib treatment. Cancer Res 2011;71(1):143–53. doi:10.​1158/​0008-5472.​CAN-10-1088.
4.
go back to reference Bombardieri E, Coliva A, Maccauro M, Seregni E, Orunesu E, Chiti A et al. Imaging of neuroendocrine tumours with gamma-emitting radiopharmaceuticals. Q J Nucl Med Mol Imaging 2010;54(1):3–15. doi:R39102241. Bombardieri E, Coliva A, Maccauro M, Seregni E, Orunesu E, Chiti A et al. Imaging of neuroendocrine tumours with gamma-emitting radiopharmaceuticals. Q J Nucl Med Mol Imaging 2010;54(1):3–15. doi:R39102241.
5.
go back to reference Pantaleo MA, Mishani E, Nanni C, Landuzzi L, Boschi S, Nicoletti G et al. Evaluation of modified PEG-anilinoquinazoline derivatives as potential agents for EGFR imaging in cancer by small animal PET. Mol Imaging Biol 2010;12(6):616–25. doi:10.1007/s11307-010-0315-z. Pantaleo MA, Mishani E, Nanni C, Landuzzi L, Boschi S, Nicoletti G et al. Evaluation of modified PEG-anilinoquinazoline derivatives as potential agents for EGFR imaging in cancer by small animal PET. Mol Imaging Biol 2010;12(6):616–25. doi:10.​1007/​s11307-010-0315-z.
7.
go back to reference Johnson JP. Cell adhesion molecules in the development and progression of malignant melanoma. Cancer Metastasis Rev 1999;18(3):345–57.PubMedCrossRef Johnson JP. Cell adhesion molecules in the development and progression of malignant melanoma. Cancer Metastasis Rev 1999;18(3):345–57.PubMedCrossRef
8.
go back to reference Gasparini G, Brooks PC, Biganzoli E, Vermeulen PB, Bonoldi E, Dirix LY, et al. Vascular integrin alpha(v)beta3: a new prognostic indicator in breast cancer. Clin Cancer Res 1998;4(11):2625–34.PubMed Gasparini G, Brooks PC, Biganzoli E, Vermeulen PB, Bonoldi E, Dirix LY, et al. Vascular integrin alpha(v)beta3: a new prognostic indicator in breast cancer. Clin Cancer Res 1998;4(11):2625–34.PubMed
10.
11.
12.
go back to reference Kenny LM, Coombes RC, Oulie I, Contractor KB, Miller M, Spinks TJ, et al. Phase I trial of the positron-emitting Arg-Gly-Asp (RGD) peptide radioligand 18F-AH111585 in breast cancer patients. J Nucl Med 2008;49(6):879–86. doi:10.2967/jnumed.107.049452.PubMedCrossRef Kenny LM, Coombes RC, Oulie I, Contractor KB, Miller M, Spinks TJ, et al. Phase I trial of the positron-emitting Arg-Gly-Asp (RGD) peptide radioligand 18F-AH111585 in breast cancer patients. J Nucl Med 2008;49(6):879–86. doi:10.​2967/​jnumed.​107.​049452.PubMedCrossRef
13.
go back to reference Glaser M, Morrison M, Solbakken M, Arukwe J, Karlsen H, Wiggen U, et al. Radiosynthesis and biodistribution of cyclic RGD peptides conjugated with novel [18F]fluorinated aldehyde-containing prosthetic groups. Bioconjug Chem 2008;19(4):951–7. doi:10.1021/bc700472w.PubMedCrossRef Glaser M, Morrison M, Solbakken M, Arukwe J, Karlsen H, Wiggen U, et al. Radiosynthesis and biodistribution of cyclic RGD peptides conjugated with novel [18F]fluorinated aldehyde-containing prosthetic groups. Bioconjug Chem 2008;19(4):951–7. doi:10.​1021/​bc700472w.PubMedCrossRef
14.
go back to reference Tomasi G, Bertoldo A, Bishu S, Unterman A, Smith CB, Schmidt KC. Voxel-based estimation of kinetic model parameters of the L-[1-(11)C]leucine PET method for determination of regional rates of cerebral protein synthesis: validation and comparison with region-of-interest-based methods. J Cereb Blood Flow Metab 2009;29(7):1317–31. doi:10.1038/jcbfm.2009.52.PubMedCrossRef Tomasi G, Bertoldo A, Bishu S, Unterman A, Smith CB, Schmidt KC. Voxel-based estimation of kinetic model parameters of the L-[1-(11)C]leucine PET method for determination of regional rates of cerebral protein synthesis: validation and comparison with region-of-interest-based methods. J Cereb Blood Flow Metab 2009;29(7):1317–31. doi:10.​1038/​jcbfm.​2009.​52.PubMedCrossRef
15.
go back to reference Bertoldo A, Vicini P, Sambuceti G, Lammertsma AA, Parodi O, Cobelli C. Evaluation of compartmental and spectral analysis models of [18F]FDG kinetics for heart and brain studies with PET. IEEE Trans Biomed Eng 1998;45(12):1429–48. doi:10.1109/10.730437.PubMedCrossRef Bertoldo A, Vicini P, Sambuceti G, Lammertsma AA, Parodi O, Cobelli C. Evaluation of compartmental and spectral analysis models of [18F]FDG kinetics for heart and brain studies with PET. IEEE Trans Biomed Eng 1998;45(12):1429–48. doi:10.​1109/​10.​730437.PubMedCrossRef
16.
go back to reference Akaike H. A new look at the statistical model identification. IEEE Trans Automat Contr 1974;19(6):716–23.CrossRef Akaike H. A new look at the statistical model identification. IEEE Trans Automat Contr 1974;19(6):716–23.CrossRef
17.
go back to reference Turkheimer FE, Hinz R, Cunningham VJ. On the undecidability among kinetic models: from model selection to model averaging. J Cereb Blood Flow Metab 2003;23(4):490–8.PubMedCrossRef Turkheimer FE, Hinz R, Cunningham VJ. On the undecidability among kinetic models: from model selection to model averaging. J Cereb Blood Flow Metab 2003;23(4):490–8.PubMedCrossRef
18.
go back to reference Cunningham VJ, Jones T. Spectral analysis of dynamic PET studies. J Cereb Blood Flow Metab 1993;13(1):15–23.PubMedCrossRef Cunningham VJ, Jones T. Spectral analysis of dynamic PET studies. J Cereb Blood Flow Metab 1993;13(1):15–23.PubMedCrossRef
19.
go back to reference Turkheimer F, Moresco RM, Lucignani G, Sokoloff L, Fazio F, Schmidt K. The use of spectral analysis to determine regional cerebral glucose utilization with positron emission tomography and [18F]fluorodeoxyglucose: theory, implementation, and optimization procedures. J Cereb Blood Flow Metab 1994;14(3):406–22.PubMedCrossRef Turkheimer F, Moresco RM, Lucignani G, Sokoloff L, Fazio F, Schmidt K. The use of spectral analysis to determine regional cerebral glucose utilization with positron emission tomography and [18F]fluorodeoxyglucose: theory, implementation, and optimization procedures. J Cereb Blood Flow Metab 1994;14(3):406–22.PubMedCrossRef
20.
go back to reference Logan J, Fowler JS, Volkow ND, Wolf AP, Dewey SL, Schlyer DJ, et al. Graphical analysis of reversible radioligand binding from time-activity measurements applied to [N-11C-methyl]-(−)-cocaine PET studies in human subjects. J Cereb Blood Flow Metab 1990;10(5):740–7.PubMedCrossRef Logan J, Fowler JS, Volkow ND, Wolf AP, Dewey SL, Schlyer DJ, et al. Graphical analysis of reversible radioligand binding from time-activity measurements applied to [N-11C-methyl]-(−)-cocaine PET studies in human subjects. J Cereb Blood Flow Metab 1990;10(5):740–7.PubMedCrossRef
22.
go back to reference DuBois DDE. A formula to estimate the approximate surface area if height and weight are known. Arch Intern Med 1916;17:863–71. DuBois DDE. A formula to estimate the approximate surface area if height and weight are known. Arch Intern Med 1916;17:863–71.
23.
go back to reference Beer AJ, Grosu AL, Carlsen J, Kolk A, Sarbia M, Stangier I, et al. [18F]galacto-RGD positron emission tomography for imaging of alphavbeta3 expression on the neovasculature in patients with squamous cell carcinoma of the head and neck. Clin Cancer Res 2007;13(22 Pt 1):6610–6. doi:10.1158/1078-0432.CCR-07-0528.PubMedCrossRef Beer AJ, Grosu AL, Carlsen J, Kolk A, Sarbia M, Stangier I, et al. [18F]galacto-RGD positron emission tomography for imaging of alphavbeta3 expression on the neovasculature in patients with squamous cell carcinoma of the head and neck. Clin Cancer Res 2007;13(22 Pt 1):6610–6. doi:10.​1158/​1078-0432.​CCR-07-0528.PubMedCrossRef
25.
go back to reference Munk OL, Bass L, Roelsgaard K, Bender D, Hansen SB, Keiding S. Liver kinetics of glucose analogs measured in pigs by PET: importance of dual-input blood sampling. J Nucl Med 2001;42(5):795–801.PubMed Munk OL, Bass L, Roelsgaard K, Bender D, Hansen SB, Keiding S. Liver kinetics of glucose analogs measured in pigs by PET: importance of dual-input blood sampling. J Nucl Med 2001;42(5):795–801.PubMed
26.
go back to reference Soo CS, Chuang VP, Wallace S, Charnsangavej C, Carrasco H. Treatment of hepatic neoplasm through extrahepatic collaterals. Radiology 1983;147(1):45–9.PubMed Soo CS, Chuang VP, Wallace S, Charnsangavej C, Carrasco H. Treatment of hepatic neoplasm through extrahepatic collaterals. Radiology 1983;147(1):45–9.PubMed
27.
go back to reference Taylor I, Bennett R, Sherriff S. The blood supply of colorectal liver metastases. Br J Cancer 1978;38(6):749–56.PubMedCrossRef Taylor I, Bennett R, Sherriff S. The blood supply of colorectal liver metastases. Br J Cancer 1978;38(6):749–56.PubMedCrossRef
28.
go back to reference Bello L, Francolini M, Marthyn P, Zhang J, Carroll RS, Nikas DC, et al. Alpha(v)beta3 and alpha(v)beta5 integrin expression in glioma periphery. Neurosurgery 2001;49(2):380–9. discussion 390.PubMed Bello L, Francolini M, Marthyn P, Zhang J, Carroll RS, Nikas DC, et al. Alpha(v)beta3 and alpha(v)beta5 integrin expression in glioma periphery. Neurosurgery 2001;49(2):380–9. discussion 390.PubMed
30.
go back to reference Beer AJ, Haubner R, Sarbia M, Goebel M, Luderschmidt S, Grosu AL, et al. Positron emission tomography using [18F]Galacto-RGD identifies the level of integrin alpha(v)beta3 expression in man. Clin Cancer Res 2006;12(13):3942–9. doi:10.1158/1078-0432.CCR-06-0266.PubMedCrossRef Beer AJ, Haubner R, Sarbia M, Goebel M, Luderschmidt S, Grosu AL, et al. Positron emission tomography using [18F]Galacto-RGD identifies the level of integrin alpha(v)beta3 expression in man. Clin Cancer Res 2006;12(13):3942–9. doi:10.​1158/​1078-0432.​CCR-06-0266.PubMedCrossRef
31.
go back to reference Battle MR, Goggi JL, Allen L, Barnett J, Morrison MS. Monitoring tumor response to antiangiogenic sunitinib therapy with 18F-fluciclatide, an 18F-labeled alphaVbeta3-integrin and alphaV beta5-integrin imaging agent. J Nucl Med 2011;52(3):424–30. doi:10.2967/jnumed.110.077479. Battle MR, Goggi JL, Allen L, Barnett J, Morrison MS. Monitoring tumor response to antiangiogenic sunitinib therapy with 18F-fluciclatide, an 18F-labeled alphaVbeta3-integrin and alphaV beta5-integrin imaging agent. J Nucl Med 2011;52(3):424–30. doi:10.​2967/​jnumed.​110.​077479.
33.
go back to reference Huang SC, Yu DC, Barrio JR, Grafton S, Melega WP, Hoffman JM, et al. Kinetics and modeling of L-6-[18F]fluoro-dopa in human positron emission tomographic studies. J Cereb Blood Flow Metab 1991;11(6):898–913. doi:10.1038/jcbfm.1991.155.PubMedCrossRef Huang SC, Yu DC, Barrio JR, Grafton S, Melega WP, Hoffman JM, et al. Kinetics and modeling of L-6-[18F]fluoro-dopa in human positron emission tomographic studies. J Cereb Blood Flow Metab 1991;11(6):898–913. doi:10.​1038/​jcbfm.​1991.​155.PubMedCrossRef
Metadata
Title
Quantification of receptor-ligand binding with [18F]fluciclatide in metastatic breast cancer patients
Authors
Giampaolo Tomasi
Laura Kenny
Francesco Mauri
Federico Turkheimer
Eric O. Aboagye
Publication date
01-12-2011
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 12/2011
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-011-1907-9

Other articles of this Issue 12/2011

European Journal of Nuclear Medicine and Molecular Imaging 12/2011 Go to the issue