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

• Published in: European journal of nuclear medicine and molecular imaging Vol. 38; no. 2; pp. 323 - 333
• Main Authors: Aide, Nicolas, Briand, Mélanie, Bohn, Pierre, Dutoit, Soizic, Lasnon, Charline, Chasle, Jacques, Rouvet, Jean, Modzelewski, Romain, Vela, Antony, Deslandes, Edwiges, Vera, Pierre, Poulain, Laurent, Carreiras, Franck
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.02.2011; Springer Verlag (Germany) [1976-....]
• Subjects: Animals; Cardiology; Cell Differentiation - drug effects; Cell Line, Tumor; Cell Transformation, Neoplastic - drug effects; Cisplatin - pharmacology; Diagnosis, Differential; Fluorodeoxyglucose F18; Humans; Imaging; Integrin alphaVbeta3 - metabolism; Male; Medicine; Medicine & Public Health; Molecular Imaging - methods; Necrosis - diagnosis; Necrosis - metabolism; Necrosis - pathology; Neoplasm, Residual - diagnosis; Neoplasm, Residual - metabolism; Neoplasm, Residual - pathology; Nuclear Medicine; Oncology; Original Article; Orthopedics; Radiology; Rats; Teratoma - diagnosis; Teratoma - metabolism; Teratoma - pathology; Testicular Neoplasms - diagnostic imaging; Testicular Neoplasms - metabolism; Testicular Neoplasms - pathology; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Tretinoin - pharmacology; α; Non-seminomatous germ cell tumour; β; expression; Residual masses; Mature teratoma; F-FDG
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-010-1624-9

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.