Lessons from 11C-Dihydrotetrabenazine Imaging in a Xenograft Mouse Model of Rat Insulinoma: is PET Imaging of Pancreatic Beta Cell Mass Feasible?
Collantes M(1), Barajas M, Quincoces G, Ramos-Membrive R, Martí-Climent JM, Ecay M, Rodriguez S, Escalada J, Penuelas I.
(1) Department of Nuclear Medicine, Clínica Universidad de Navarra, Pamplona, Spain.
The feasibility of beta cell mass (BCM) imaging and quantification with positron emission tomography (PET) in the pancreas is controversial. In an effort to shed some light on this topic, we have used a xenograft model of rat insulinoma (RIN) in mice, mimicking an intramuscular islet transplantation situation.
105 RIN cells were subcutaneously implanted in nude mice (n=8). Tumour size and glycaemia levels were determined daily. Rat C-peptide was measured to demonstrate rat insulin production. PET imaging with 1 1 C-(+)-α--dihidrotetrabenazine (1 1 C--DTBZ) was done at 3 and 4 weeks and compared with 1 8 F--FDG and 1 8 F-DOPA studies in the same mice. Ex--vivo autoradiography with 1 1 C--DTBZ was carried out in frozen sections of tumours. VMAT2 expression was measured by Western--blot and immunohistochemistry in tumours and RIN cells.
Functional rat insulin production in mice was demonstrated by substantial decrease in glycaemia (<50 mg/dL by week 4) and rat C--peptide levels (7.2±2.6ng/mL) similar to those measured in control rats. PET studies showed that tumour imaging with 1 1 C---DTBZ at four (n=8) and five (n=5) weeks was negative; only bigger tumours could be seen with 1 8 F-DOPA. In explanted tumours 1 1 C-DTBZ autoradiography was negative, albeit VMAT2 expression measured by Western--blotand immunohistochemistry was lower than in cultured RIN cells.
Although insulinomas are fully functional it does not seem feasible to use 11 C--DTBZ for i n vivo measuring of BCM. This might either be due to inherent technical limitations of PET, decrease in VMAT2 expression in the tumours due to unknown reasons, or other biological limiting facts.
CITATION Q J Nucl Med Mol Imaging. 2015 Apr 17.