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.
OBJECTIVE
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.


CONCLUSIONS
Imaging α(v)β(3) integrin accurately distinguished mature teratoma from necrosis following cisplatin-based treatment in human NSGCT xenografts.
Aide
Nicolas
N
EA1772, IFR 146 ICORE, GRECAN, François Baclesse Cancer Centre and Caen University, Caen, France. n.aide@baclesse.fr
Briand
Mélanie
M
Bohn
Pierre
P
Dutoit
Soizic
S
Lasnon
Charline
C
Chasle
Jacques
J
Rouvet
Jean
J
Modzelewski
Romain
R
Vela
Antony
A
Deslandes
Edwiges
E
Vera
Pierre
P
Poulain
Laurent
L
Carreiras
Franck
F
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003937:Diagnosis, Differential; D019788:Fluorodeoxyglucose F18; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D009336:Necrosis / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D051381:Rats; D013724:Teratoma / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D013736:Testicular Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D014212:Tretinoin / Q000494:pharmacology
D039302:Integrin alphaVbeta3; D019788:Fluorodeoxyglucose F18; D014212:Tretinoin; D002945:Cisplatin