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

01.12.2011 | Original Article

Differential diagnosis of solitary pulmonary nodules using 99mTc-3P4-RGD2 scintigraphy

verfasst von: Qingjie Ma, Bin Ji, Bing Jia, Shi Gao, Tiefeng Ji, Xueju Wang, Zhenguo Han, Guoqing Zhao

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 12/2011

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Targeting of integrin ανβ3 with molecular imaging agents offers great potential in early detection and monitoring of tumour angiogenesis. Recently, an RGD (Arg-Gly-Asp) tracer, 99mTc-3P4-RGD2, with high affinity to integrin ανβ3 and in vivo tumour uptake was developed. In this study, we evaluate the feasibility of this novel radiotracer in the noninvasive differentiation of solitary pulmonary nodules (SPNs).

Methods

Twenty-one patients with SPNs on CT were studied scintigraphically after administration of 99mTc-3P4-RGD2 with a dose of 939 ± 118 MBq. Image interpretation using a 5-point scale was performed by one thoracic radiologist for CT and three nuclear medicine radiologists for single photon emission computed tomography (SPECT). Scintigraphic images were also analysed semiquantitatively by calculating tumour to normal tissue ratio (T/N). The “gold standard” was based on the histopathological diagnosis of the surgical samples from all recruited patients. A fraction of the samples were analysed immunohistochemically for integrin αvβ3 expression.

Results

Among the 21 SPNs, 15 (71%) were diagnosed as malignant and 6 (29%) were benign. The mean size for SPNs was 2.2 ± 0.6 cm. The sensitivity and specificity for CT interpretation, SPECT visual and semiquantitative analysis were 80/67%, 100/67% and 100/67%, respectively. All SPNs classified as indeterminate by CT were correctly diagnosed by 99mTc-3P4-RGD2 scintigraphy. The empirical receiver-operating characteristic (ROC) areas were 0.811 [95% confidence interval (CI) 58–95%] for CT, 0.833 (95% CI 61–96%) for SPECT and 0.844 (95% CI 62–96%) for T/N ratios, respectively. Immunohistochemistry confirmed ανβ3 expression in malignant and benign nodules with uptake in 99mTc-3P4-RGD2 scintigraphy.

Conclusion

In this first-in-human study, we demonstrated the feasibility of using 99mTc-3P4-RGD2 scintigraphy in differentiating SPNs. This procedure appears to be highly sensitive in detection of malignant SPNs. SPECT visual analysis seems to be sufficient for characterization of SPNs.
Literatur
1.
Zurück zum Zitat Gould MK, Sanders GD, Barnett PG, Rydzak CE, Maclean CC, McClellan MB, et al. Cost-effectiveness of alternative management strategies for patients with solitary pulmonary nodules. Ann Intern Med 2003;138(9):724–35.PubMed Gould MK, Sanders GD, Barnett PG, Rydzak CE, Maclean CC, McClellan MB, et al. Cost-effectiveness of alternative management strategies for patients with solitary pulmonary nodules. Ann Intern Med 2003;138(9):724–35.PubMed
3.
Zurück zum Zitat Rohren EM, Lowe VJ. Update in PET imaging of nonsmall cell lung cancer. Semin Nucl Med 2004;34(2):134–53.PubMed Rohren EM, Lowe VJ. Update in PET imaging of nonsmall cell lung cancer. Semin Nucl Med 2004;34(2):134–53.PubMed
5.
Zurück zum Zitat Rebollo AC, Jiménez-Hoyuela JM, Martínez del Valle MD Martinez, Fernández Aguirre C, Soria C, Velasco JL. [Lung scintigraphy with technetium 99m depreotide in the assessment of solitary pulmonary nodules]. Arch Bronconeumol 2004;40(11):534–6.PubMed Rebollo AC, Jiménez-Hoyuela JM, Martínez del Valle MD Martinez, Fernández Aguirre C, Soria C, Velasco JL. [Lung scintigraphy with technetium 99m depreotide in the assessment of solitary pulmonary nodules]. Arch Bronconeumol 2004;40(11):534–6.PubMed
6.
Zurück zum Zitat Plachcińska A, Mikołajczak R, Maecke HR, Michalski A, Rzeszutek K, Kozak J, et al. 99mTc-EDDA/HYNIC-TOC scintigraphy in the differential diagnosis of solitary pulmonary nodules. Eur J Nucl Med Mol Imaging 2004;31(7):1005–10. doi:10.1007/s00259-004-1511-3.PubMed Plachcińska A, Mikołajczak R, Maecke HR, Michalski A, Rzeszutek K, Kozak J, et al. 99mTc-EDDA/HYNIC-TOC scintigraphy in the differential diagnosis of solitary pulmonary nodules. Eur J Nucl Med Mol Imaging 2004;31(7):1005–10. doi:10.​1007/​s00259-004-1511-3.PubMed
7.
Zurück zum Zitat Spanu A, Schillaci O, Pirina P, Arru A, Madeddu G, Chessa F, et al. 99mTc-tetrofosmin SPECT in solitary pulmonary nodule evaluation. Oncol Rep 2006;16(4):763–9.PubMed Spanu A, Schillaci O, Pirina P, Arru A, Madeddu G, Chessa F, et al. 99mTc-tetrofosmin SPECT in solitary pulmonary nodule evaluation. Oncol Rep 2006;16(4):763–9.PubMed
8.
Zurück zum Zitat Niu G, Chen X. Why integrin as a primary target for imaging and therapy. Theranostics 2011;1:30–47.PubMed Niu G, Chen X. Why integrin as a primary target for imaging and therapy. Theranostics 2011;1:30–47.PubMed
9.
Zurück zum Zitat Chen X, Sievers E, Hou Y, Park R, Tohme M, Bart R, et al. Integrin alpha v beta 3-targeted imaging of lung cancer. Neoplasia 2005;7(3):271–9. doi:10.1593/neo.04538.PubMed Chen X, Sievers E, Hou Y, Park R, Tohme M, Bart R, et al. Integrin alpha v beta 3-targeted imaging of lung cancer. Neoplasia 2005;7(3):271–9. doi:10.​1593/​neo.​04538.PubMed
10.
Zurück zum Zitat Jia B, Liu Z, Zhu Z, Shi J, Jin X, Zhao H, et al. Blood clearance kinetics, biodistribution, and radiation dosimetry of a kit-formulated integrin alpha(v)beta (3)-selective radiotracer (99m)Tc-3PRGD (2) in non-human primates. Mol Imaging Biol 2011;13(4):730–6. doi:10.1007/s11307-010-0385-y.PubMed Jia B, Liu Z, Zhu Z, Shi J, Jin X, Zhao H, et al. Blood clearance kinetics, biodistribution, and radiation dosimetry of a kit-formulated integrin alpha(v)beta (3)-selective radiotracer (99m)Tc-3PRGD (2) in non-human primates. Mol Imaging Biol 2011;13(4):730–6. doi:10.​1007/​s11307-010-0385-y.PubMed
11.
Zurück zum Zitat Wang L, Shi J, Kim YS, Zhai S, Jia B, Zhao H, et al. Improving tumor-targeting capability and pharmacokinetics of (99m)Tc-labeled cyclic RGD dimers with PEG(4) linkers. Mol Pharm 2009;6(1):231–45. doi:10.1021/mp800150r.PubMed Wang L, Shi J, Kim YS, Zhai S, Jia B, Zhao H, et al. Improving tumor-targeting capability and pharmacokinetics of (99m)Tc-labeled cyclic RGD dimers with PEG(4) linkers. Mol Pharm 2009;6(1):231–45. doi:10.​1021/​mp800150r.PubMed
12.
Zurück zum Zitat Zhang X, Xiong Z, Wu Y, Cai W, Tseng JR, Gambhir SS, et al. Quantitative PET imaging of tumor integrin alphavbeta3 expression with 18F-FRGD2. J Nucl Med 2006;47(1):113–21.PubMed Zhang X, Xiong Z, Wu Y, Cai W, Tseng JR, Gambhir SS, et al. Quantitative PET imaging of tumor integrin alphavbeta3 expression with 18F-FRGD2. J Nucl Med 2006;47(1):113–21.PubMed
13.
Zurück zum Zitat Liu Z, Jia B, Shi J, Jin X, Zhao H, Li F et al. Tumor uptake of the RGD dimeric probe (99m)Tc-G(3)-2P(4)-RGD2 is correlated with integrin alpha(v)beta(3) expressed on both tumor cells and neovasculature. Bioconjug Chem 2010. doi:10.1021/bc900547d. Liu Z, Jia B, Shi J, Jin X, Zhao H, Li F et al. Tumor uptake of the RGD dimeric probe (99m)Tc-G(3)-2P(4)-RGD2 is correlated with integrin alpha(v)beta(3) expressed on both tumor cells and neovasculature. Bioconjug Chem 2010. doi:10.​1021/​bc900547d.
14.
Zurück zum Zitat 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.PubMed 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.PubMed
15.
Zurück zum Zitat Bach-Gansmo T, Danielsson R, Saracco A, Wilczek B, Bogsrud TV, Fangberget A, et al. Integrin receptor imaging of breast cancer: a proof-of-concept study to evaluate 99mTc-NC100692. J Nucl Med 2006;47(9):1434–9.PubMed Bach-Gansmo T, Danielsson R, Saracco A, Wilczek B, Bogsrud TV, Fangberget A, et al. Integrin receptor imaging of breast cancer: a proof-of-concept study to evaluate 99mTc-NC100692. J Nucl Med 2006;47(9):1434–9.PubMed
16.
Zurück zum Zitat 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.PubMed 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.PubMed
18.
Zurück zum Zitat Liu S. Radiolabeled cyclic RGD peptides as integrin alpha(v)beta(3)-targeted radiotracers: maximizing binding affinity via bivalency. Bioconjug Chem 2009;20(12):2199–213. doi:10.1021/bc900167c.PubMed Liu S. Radiolabeled cyclic RGD peptides as integrin alpha(v)beta(3)-targeted radiotracers: maximizing binding affinity via bivalency. Bioconjug Chem 2009;20(12):2199–213. doi:10.​1021/​bc900167c.PubMed
20.
Zurück zum Zitat Viggiano RW, Swensen SJ, Rosenow 3rd EC. Evaluation and management of solitary and multiple pulmonary nodules. Clin Chest Med 1992;13(1):83–95.PubMed Viggiano RW, Swensen SJ, Rosenow 3rd EC. Evaluation and management of solitary and multiple pulmonary nodules. Clin Chest Med 1992;13(1):83–95.PubMed
21.
Zurück zum Zitat Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA 2001;285(7):914–24.PubMed Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA 2001;285(7):914–24.PubMed
22.
Zurück zum Zitat Kim SK, Allen-Auerbach M, Goldin J, Fueger BJ, Dahlbom M, Brown M, et al. Accuracy of PET/CT in characterization of solitary pulmonary lesions. J Nucl Med 2007;48(2):214–20.PubMed Kim SK, Allen-Auerbach M, Goldin J, Fueger BJ, Dahlbom M, Brown M, et al. Accuracy of PET/CT in characterization of solitary pulmonary lesions. J Nucl Med 2007;48(2):214–20.PubMed
23.
Zurück zum Zitat Beyer T, Townsend DW, Brun T, Kinahan PE, Charron M, Roddy R, et al. A combined PET/CT scanner for clinical oncology. J Nucl Med 2000;41(8):1369–79.PubMed Beyer T, Townsend DW, Brun T, Kinahan PE, Charron M, Roddy R, et al. A combined PET/CT scanner for clinical oncology. J Nucl Med 2000;41(8):1369–79.PubMed
25.
Zurück zum Zitat Higashi K, Ueda Y, Seki H, Yuasa K, Oguchi M, Noguchi T, et al. Fluorine-18-FDG PET imaging is negative in bronchioloalveolar lung carcinoma. J Nucl Med 1998;39(6):1016–20.PubMed Higashi K, Ueda Y, Seki H, Yuasa K, Oguchi M, Noguchi T, et al. Fluorine-18-FDG PET imaging is negative in bronchioloalveolar lung carcinoma. J Nucl Med 1998;39(6):1016–20.PubMed
26.
Zurück zum Zitat Brooks PC, Clark RA, Cheresh DA. Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science 1994;264(5158):569–71.PubMed Brooks PC, Clark RA, Cheresh DA. Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science 1994;264(5158):569–71.PubMed
28.
Zurück zum Zitat Antonov AS, Antonova GN, Munn DH, Mivechi N, Lucas R, Catravas JD, et al. alphaVbeta3 integrin regulates macrophage inflammatory responses via PI3 kinase/Akt-dependent NF-kappaB activation. J Cell Physiol 2011;226(2):469–76. doi:10.1002/jcp.22356.PubMed Antonov AS, Antonova GN, Munn DH, Mivechi N, Lucas R, Catravas JD, et al. alphaVbeta3 integrin regulates macrophage inflammatory responses via PI3 kinase/Akt-dependent NF-kappaB activation. J Cell Physiol 2011;226(2):469–76. doi:10.​1002/​jcp.​22356.PubMed
Metadaten
Titel
Differential diagnosis of solitary pulmonary nodules using 99mTc-3P4-RGD2 scintigraphy
verfasst von
Qingjie Ma
Bin Ji
Bing Jia
Shi Gao
Tiefeng Ji
Xueju Wang
Zhenguo Han
Guoqing Zhao
Publikationsdatum
01.12.2011
Verlag
Springer-Verlag
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 12/2011
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-011-1901-2

Weitere Artikel der Ausgabe 12/2011

European Journal of Nuclear Medicine and Molecular Imaging 12/2011 Zur Ausgabe