Search

PurposeWe assessed whether imaging αvβ3 integrin could distinguish mature teratoma from necrosis in human non-seminomatous germ cell tumour (NSGCT) post-chemotherapy residual masses.MethodsHuman 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).18F-Fluorodeoxyglucose (18F-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 αvβ3 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 [99mTc]HYNIC-RGD [6-hydrazinonicotinic acid conjugated to cyclo(Arg-Gly-Asp-D-Phe-Lys)]. Correlative immunohistochemistry studies of human and mouse αvβ3 expression were performed.ResultsCisplatin+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 18F-FDG [mean standardised uptake value (SUVmean) = 0.48 ± 0.05] compared to untreated embryonal carcinoma (SUVmean = 0.92 ± 0.13) (p = 0.005). αvβ3 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 αvβ3 integrin expression was strong in the glandular structures of mature teratoma lesions and negative in host stroma.ConclusionImaging αvβ3 integrin accurately distinguished mature teratoma from necrosis following cisplatin-based treatment in human NSGCT xenografts. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the usefulness of FDG PET in the early prediction of the effects of chemotherapy on human testicular cancer xenografts. Nude rats bearing subcutaneous human embryonal carcinoma xenografts received either cisplatin (5 mg/kg) or saline serum. Small-animal PET studies were performed on days 0, 2, 4 and 7 and compared to immunochemistry studies, flow cytometry studies and hexokinase assays. Cisplatin treatment resulted in biphasic FDG uptake evolution: a peak was observed on day 2, followed by a marked decrease on day 7 despite an insignificant change in tumour volume. Similarly, a peak in cyclin A immunostaining was observed on days 2 and 4), followed by a significant decrease on day 7. Flow cytometry showed that the cyclin A peak was not related to increased cell proliferation but was due to a transient S and G2/M cell cycle arrest. A marked increase in cell apoptosis was observed from day 2 to day 7. GLUT-1 showed a significant decrease on day 7. Macrophagic infiltrate remained stable except for an increase observed on day 7. In control tumours, continuous growth was observed, all immunostaining markers remaining stable over time. Hexokinase activity was significantly lower on day 7 in treated tumours than in controls. FDG PET may be useful in the early evaluation of treatment in patients with testicular cancer. In our model, a very early increased [18F]-FDG uptake was related to a transient cell cycle arrest and early stage apoptosis but did not reveal refractory disease. [ABSTRACT FROM AUTHOR]