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01-09-2008 | Brief Article

Usefulness of Automatic Quantification of Immunochemical Staining on Whole Tumor Sections for Correlation with Oncological Small Animal PET Studies: An Example with Cell Proliferation, Glucose Transporter 1 and FDG

Authors: Nicolas Aide, Alexandre Labiche, Paulette Herlin, Maria Paciencia, Laurent Poulain, Soizic Dutoit, Françoise Montravers, Pascal Gauduchon, Jacques Chasle

Published in: Molecular Imaging and Biology | Issue 5/2008

Abstract

Aim

To highlight the use of automatic quantification of immunochemical staining on digitized images of whole tumor sections in preclinical positron emission tomography (PET) studies.

Materials and methods

Xenografted human testicular tumors (36) were imaged with 2-deoxy-2[F-18]fluoro-d-glucose (FDG) small animal PET (SA-PET). Tumor cell proliferation and glucose transportation were assessed with cyclin A and Glut-1 immunostaining. Tumor slides were digitized and processed with PixCyt^® software enabling whole slide quantification, then compared with junior and senior pathologist manual scoring. Manual and automatic quantification results were correlated to FDG uptake.

Results

For cyclin A, inter- and intra-observer agreement for manual scoring was 0.52 and 0.72 and concordance between senior pathologist and automatic quantification was 0.84. Correlations between Tumor/Background ratio and tumor cell proliferation assessed by automatic quantification, junior and senior pathologists were 0.75, 0.55, and 0.61, respectively. Correlation between Tumor/Background ratio and Glut-1 assessed by automatic quantification was 0.74.

Conclusion

Automatic quantification of immunostaining is a valuable tool to overcome inter- and intra-observer variability for correlation of cell proliferation or other markers with tumor tracer uptake.

Nanni C, Di Leo K, Tonelli R et al (2007) FDG small animal PET permits early detection of malignant cells in a xenograft murine model. Eur J Nucl Med Mol Imaging 34:755–762PubMedCrossRef

Aliaga A, Rousseau JA, Cadorette J et al (2007) A small animal positron emission tomography study of the effect of chemotherapy and hormonal therapy on the uptake of 2-deoxy-2-[F-18]fluoro-d-glucose in murine models of breast cancer. Mol Imaging Biol 9:144–150PubMedCrossRef

Cullinane C, Dorow DS, Kansara M et al (2005) An in vivo tumor model exploiting metabolic response as a biomarker for targeted drug development. Cancer Res 65:9633–9636PubMedCrossRef

Dorow DS, Cullinane C, Conus N et al (2006) Multi-tracer small animal PET imaging of the tumour response to the novel pan-Erb-B inhibitor CI-1033. Eur J Nucl Med Mol Imaging 33:441–452PubMedCrossRef

Nanni C, Rubello D, Khan S, Al Nahhas A, Fanti S (2007) Role of small animal PET in stimulating the development of new radiopharmaceuticals in oncology. Nucl Med Commun 28:427–429PubMedCrossRef

Nanni C, Rubello D, Fanti S (2007) Role of small animal PET for molecular imaging in pre-clinical studies. Eur J Nucl Med Mol Imaging 34:1819–1822PubMedCrossRef

Molthoff CF, Klabbers BM, Berkhof J et al (2007) Monitoring response to radiotherapy in human squamous cell cancer bearing nude mice: comparison of 2¢-deoxy-2¢-[(18)F]fluoro-d:-glucose (FDG) and 3¢-[(18)F]fluoro-3¢-deoxythymidine (FLT). Mol Imaging Biol 9:340–347PubMedCrossRef

Brepoels L, Stroobants S, Vandenberghe P et al (2007) Effect of corticosteroids on 18F-FDG uptake in tumor lesions after chemotherapy. J Nucl Med 48:390–397PubMed

Leyton J, Latigo JR, Perumal M, Dhaliwal H, He Q, Aboagye EO (2005) Early detection of tumor response to chemotherapy by 3¢-deoxy-3¢-[18F]fluorothymidine positron emission tomography: the effect of cisplatin on a fibrosarcoma tumor model in vivo. Cancer Res 65:4202–4210PubMedCrossRef

10.

Huisman MC, Reder S, Weber AW, Ziegler SI, Schwaiger M (2006) Performance evaluation of the Philips MOSAIC small animal PET scanner. Eur J Nucl Med Mol Imaging 34:532–540PubMedCrossRef

11.

Chiang S, Cardi C, Matej S et al (2004) Clinical validation of fully 3-D versus 2.5-D RAMLA reconstruction on the Philips-ADAC CPET PET scanner. Nucl Med Commun 25:1103–1107PubMedCrossRef

12.

Aide N, Louis MH, Dutoit S et al (2007) Improvement of semi-quantitative small-animal PET data with recovery coefficients: a phantom and rat study. Nucl Med Commun 28:813–822PubMedCrossRef

13.

Calvet L, Geoerger B, Regairaz M et al (2006) Pleiotrophin, a candidate gene for poor tumor vasculature and in vivo neuroblastoma sensitivity to irinotecan. Oncogene 25:3150–3159PubMedCrossRef

14.

Elie N, Plancoulaine B, Signolle JP, Herlin P (2003) A simple way of quantifying immunostained cell nuclei on the whole histologic section. Cytometry A 56:37–45PubMedCrossRef

15.

Elie N, Kaliski A, Peronneau P, Opolon P, Roche A, Lassau N (2007) Methodology for quantifying interactions between perfusion evaluated by DCE-US and hypoxia throughout tumor growth. Ultrasound Med Biol 33:549–560PubMedCrossRef

16.

Galaup A, Cazes A, Le Jan S et al (2006) Angiopoietin-like 4 prevents metastasis through inhibition of vascular permeability and tumor cell motility and invasiveness. Proc Natl Acad Sci U S A 103:18721–18726PubMedCrossRef

17.

Vesselle H, Schmidt RA, Pugsley JM et al (2000) Lung cancer proliferation correlates with [F-18]fluorodeoxyglucose uptake by positron emission tomography. Clin Cancer Res 6:3837–3844PubMed

18.

Howard CV, Reed MG (1998) Unbiased stereology: three-dimensional measurement in microscopy. BIOS Scientific, London

19.

Riedl CC, Akhurst T, Larson S et al (2007) 18F-FDG PET scanning correlates with tissue markers of poor prognosis and predicts mortality for patients after liver resection for colorectal metastases. J Nucl Med 48:771–775PubMedCrossRef

20.

Yamamoto Y, Nishiyama Y, Ishikawa S et al (2007) Correlation of (18)F-FLT and (18)F-FDG uptake on PET with Ki-67 immunohistochemistry in non-small cell lung cancer. Eur J Nucl Med Mol Imaging 34:1610–1616PubMedCrossRef

21.

Aide N, Briand M, Dutoit S et al (2007) Early evaluation of chemotherapy effect with longitudinal fluorodeoxyglucose (FDG) small animal PET (SA-PET) in human testicular cancer xenografts. Eur J Nucl Med Mol Imaging 34:S298

22.

Desdouets C, Sobczak-Thepot J, Murphy M, Brechot C (1995) Cyclin A: function and expression during cell proliferation. Prog Cell Cycle Res 1:115–123PubMed

23.

Yam CH, Fung TK, Poon RY (2002) Cyclin A in cell cycle control and cancer. Cell Mol Life Sci 59:1317–1326PubMedCrossRef

24.

Ishibashi H, Suzuki T, Suzuki S et al (2005) Progesterone receptor in non-small cell lung cancer—a potent prognostic factor and possible target for endocrine therapy. Cancer Res 65:6450–6458PubMedCrossRef

25.

Kubota R, Yamada S, Kubota K, Ishiwata K, Tamahashi N, Ido T (1992) Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography. J Nucl Med 33:1972–1980PubMed

Title: Usefulness of Automatic Quantification of Immunochemical Staining on Whole Tumor Sections for Correlation with Oncological Small Animal PET Studies: An Example with Cell Proliferation, Glucose Transporter 1 and FDG
Authors: Nicolas Aide
Alexandre Labiche
Paulette Herlin
Maria Paciencia
Laurent Poulain
Soizic Dutoit
Françoise Montravers
Pascal Gauduchon
Jacques Chasle
Publication date: 01-09-2008
Publisher: Springer-Verlag
Published in: Molecular Imaging and Biology / Issue 5/2008
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-008-0144-5

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Usefulness of Automatic Quantification of Immunochemical Staining on Whole Tumor Sections for Correlation with Oncological Small Animal PET Studies: An Example with Cell Proliferation, Glucose Transporter 1 and FDG

Abstract

Aim

Materials and methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Aim

Materials and methods

Results

Conclusion

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