RT Journal Article
SR Electronic
T1 Pharmacological evaluation of the peripheral benzodiazepine receptor radioligand [<sup>123</sup>I]-CLINDE in a breast tumour model
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1108
OP 1108
VO 51
IS supplement 2
A1 Mattner, Filomena
A1 Pham, Tien
A1 Berghofer, Paula
A1 Howell, Nicholas
A1 Bourdier, Thomas
A1 Rahardjo, Gita
A1 Kench, Peter
A1 Zahra, David
A1 Gregoire, Marie
A1 Katsifis, Andrew
YR 2010
UL http://jnm.snmjournals.org/content/51/supplement_2/1108.abstract
AB 1108 Objectives The aim of this study was to evaluate the peripheral benzodiazepine receptor ligand [123/125I]-CLINDE in breast tumour bearing rodents. Methods Balb/c nude mice bearing the MDA-MB-231 human breast adenocarcinoma were administered with [123/125I]-CLINDE intravenously by the tail vein and biodistribution, competition, metabolite analysis, autoradiography and imaging studies were undertaken 33-36 days after tumour induction. For biodistribution the mice were sacrificed between 0.5 to 24h p.i. Drug competition studies were undertaken with PK11195 and CLINDE. [123I]-CLINDE stability in tissue and plasma were measured by HPLC and Radio-TLC. PBR expression in MDA cells and tumour tissue were assessed by ligand binding assays and RT-PCR. Imaging was performed on an X-SPECT/CT animal imaging system. Results PBR binding of [125I]-CLINDE in tumours indicated high affinity for PBR (Kd ≈1nM) and Bmax of 11 pmol/mg protein. PBR expression in the cells and tumours was confirmed by RT-PCR. Biodistribution indicated uptake of 0.9-1.6%ID/g in tumour. Pre-administration of PK 11195 at a dose of 1mg/Kg reduced the uptake of activity in all organs with PBR expression except in adrenals and tumour. The tumour to blood ratio increased with time reaching 6 at 24h. Autoradiography showed a heterogeneous distribution of the uptake in the tumour. γ-Imaging of [123I]-CLINDE indicated significant contrast in the tumours compared to normal tissue. Metabolite studies indicated that the activity extracted from tumours was the intact [123I]-CLINDE. Conclusions PBR expression has been confirmed in MDA-MB-231 human breast adenocarcinoma tumours using tracer uptake and RT-PCR studies. The PBR imidazopyridine ligand [123/125I]-CLINDE is a suitable tracer to study the role and relevance of the PBR in tumours