alpha(v)beta(3) imaging can accurately distinguish between mature teratoma and necrosis in F-18-FDG-negative residual masses after treatment of non-seminomatous testicular cancer: a preclinical study

作者:Aide Nicolas*; Briand Melanie; Bohn Pierre; Dutoit Soizic; Lasnon Charline; Chasle Jacques; Rouvet Jean; Modzelewski Romain; Vela Antony; Deslandes Edwiges; Vera Pierre; Poulain Laurent; Carreiras Franck
来源:European Journal of Nuclear Medicine and Molecular Imaging, 2011, 38(2): 323-333.
DOI:10.1007/s00259-010-1624-9

摘要

We assessed whether imaging alpha(v)beta(3) integrin could distinguish mature teratoma from necrosis in human non-seminomatous germ cell tumour (NSGCT) post-chemotherapy residual masses.
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).F-18-Fluorodeoxyglucose (F-18-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 alpha(v)beta(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 [Tc-99m]HYNIC-RGD [6-hydrazinonicotinic acid conjugated to cyclo(Arg-Gly-Asp-D-Phe-Lys)]. Correlative immunohistochemistry studies of human and mouse alpha(v)beta(3) expression were performed.
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 F-18-FDG [mean standardised uptake value (SUVmean) = 0.48 +/- 0.05] compared to untreated embryonal carcinoma (SUVmean = 0.92 +/- 0.13) (p = 0.005). alpha(v)beta(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 alpha(v)beta(3) integrin expression was strong in the glandular structures of mature teratoma lesions and negative in host stroma.
Imaging alpha(v)beta(3) integrin accurately distinguished mature teratoma from necrosis following cisplatin-based treatment in human NSGCT xenografts.

  • 出版日期2011-2