FDG PET imaging of Ela1-myc mice reveals major biological differences between pancreatic acinar and ductal tumours.
OBJECTIVE
The aim was to evaluate FDG PET imaging in Ela1-myc mice, a pancreatic cancer model resulting in the development of tumours with either acinar or mixed acinar-ductal phenotype.


METHODS
Transversal and longitudinal FDG PET studies were conducted; selected tissue samples were subjected to autoradiography and ex vivo organ counting. Glucose transporter and hexokinase mRNA expression was analysed by quantitative reverse transcription polymerase chain reaction (RT-PCR); Glut2 expression was analysed by immunohistochemistry.


RESULTS
Transversal studies showed that mixed acinar-ductal tumours could be identified by FDG PET several weeks before they could be detected by hand palpation. Longitudinal studies revealed that ductal--but not acinar--tumours could be detected by FDG PET. Autoradiographic analysis confirmed that tumour areas with ductal differentiation incorporated more FDG than areas displaying acinar differentiation. Ex vivo radioactivity measurements showed that tumours of solely acinar phenotype incorporated more FDG than pancreata of non-transgenic littermates despite the fact that they did not yield positive PET images. To gain insight into the biological basis of the differential FDG uptake, glucose transporter and hexokinase transcript expression was studied in microdissected tumour areas enriched for acinar or ductal cells and validated using cell-specific markers. Glut2 and hexokinase I and II mRNA levels were up to 20-fold higher in ductal than in acinar tumours. Besides, Glut2 protein overexpression was found in ductal neoplastic cells but not in the surrounding stroma.


CONCLUSIONS
In Ela1-myc mice, ductal tumours incorporate significantly more FDG than acinar tumours. This difference likely results from differential expression of Glut2 and hexokinases. These findings reveal previously unreported biological differences between acinar and ductal pancreatic tumours.
Abasolo
Ibane
I
Institut Municipal d'Investigació Mèdica-Hospital del Mar, Parc de Recerca Biomèdica de Barcelona, Carrer del Dr. Aiguader, 88, 08003, Barcelona, Spain.
Pujal
Judit
J
Rabanal
Rosa M
RM
Serafin
Anna
A
Navarro
Pilar
P
Millán
Olga
O
Real
Francisco X
FX
D000818:Animals; D018267:Carcinoma, Acinar Cell / Q000000981:diagnostic imaging* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000000981:diagnostic imaging* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D000075065:Elongin; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics; D006593:Hexokinase / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D049268:Positron-Emission Tomography; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics
D000075065:Elongin; D051246:Glucose Transport Proteins, Facilitative; D012333:RNA, Messenger; D014157:Transcription Factors; D019788:Fluorodeoxyglucose F18; D006593:Hexokinase