αvβ3 imaging can accurately distinguish between mature teratoma and necrosis in 18F-FDG-negative residual masses after treatment of non-seminomatous testicular cancer: a preclinical study.

Abstract

PURPOSE:

We assessed whether imaging α(v)β(3) integrin could distinguish mature teratoma from necrosis in human non-seminomatous germ cell tumour (NSGCT) post-chemotherapy residual masses.

METHODS:

Human embryonal carcinoma xenografts (six/rat) were untreated (controls) or treated to form mature teratomas with low-dose cisplatin and all-trans retinoic acid (ATRA) over a period of 8 weeks. In another group, necrosis was induced in xenografts with high-dose cisplatin plus etoposide (two cycles). (18)F-Fluorodeoxyglucose ((18)F-FDG) small animal positron emission tomography (SA PET) imaging was performed in three rats (one control and two treated for 4 and 8 weeks with cisplatin+ATRA). Imaging of α(v)β(3) expression was performed in six rats bearing mature teratomas and two rats with necrotic lesions on a microSPECT/CT device after injection of the tracer [(99m)Tc]HYNIC-RGD [6-hydrazinonicotinic acid conjugated to cyclo(Arg-Gly-Asp-D-Phe-Lys)]. Correlative immunohistochemistry studies of human and mouse α(v)β(3) expression were performed.

RESULTS:

Cisplatin+ATRA induced differentiation of the xenografts. After 8 weeks, some glandular structures and mesenchymal cells were visible; in contrast, control tumours showed undifferentiated tissues. SA PET imaging showed that mature teratoma had very low avidity for (18)F-FDG [mean standardised uptake value (SUV(mean)) = 0.48 ± 0.05] compared to untreated embryonal carcinoma (SUV(mean) = 0.92 ± 0.13) (p = 0.005). α(v)β(3) imaging accurately distinguished mature teratoma (tumour to muscle ratio = 4.29 ± 1.57) from necrosis (tumour to muscle ratio = 1.3 ± 0.26) (p = 0.0002). Immunohistochemistry studies showed that α(v)β(3) integrin expression was strong in the glandular structures of mature teratoma lesions and negative in host stroma.

CONCLUSION:

Imaging α(v)β(3) integrin accurately distinguished mature teratoma from necrosis following cisplatin-based treatment in human NSGCT xenografts.

• Authors: Nicolas Aide, Mélanie Briand, Pierre Bohn, Soizic Dutoit, Charline Lasnon, Jacques Chasle, Jean Rouvet, Romain Modzelewski, Antony Vela, Edwiges Deslandes, Pierre Vera, Laurent Poulain, Franck Carreiras
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 38 Issue 2 Pg. 323-33 (Feb 2011) ISSN: 1619-7089 [Electronic] Germany
• PMID: 20882281 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Integrin alphaVbeta3
• Fluorodeoxyglucose F18
• Tretinoin
• Cisplatin

Topics

• Animals
• Cell Differentiation (drug effects)
• Cell Line, Tumor
• Cell Transformation, Neoplastic (drug effects)
• Cisplatin (pharmacology)
• Diagnosis, Differential
• Fluorodeoxyglucose F18
• Humans
• Integrin alphaVbeta3 (metabolism)
• Male
• Molecular Imaging (methods)
• Necrosis (diagnosis, metabolism, pathology)
• Neoplasm, Residual (diagnosis, metabolism, pathology)
• Rats
• Teratoma (diagnosis, metabolism, pathology)
• Testicular Neoplasms (diagnostic imaging, metabolism, pathology)
• Tomography, Emission-Computed, Single-Photon
• Tomography, X-Ray Computed
• Tretinoin (pharmacology)