Rapid Reduction of 
1-Receptor Binding and 18F-FDG Uptake in Rat Gliomas After In Vivo Treatment with Doxorubicin
Aren van Waarde 1*,
Kazuhiro Shiba 2,
Johan R. de Jong 1,
Kiichi Ishiwata 3,
Rudi A. Dierckx 1,
and
Philip H. Elsinga 1
1 Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
2 Division of Tracer Kinetics, Advanced Science Research Center, Central Institute of Radioisotopes Science, Kanazawa University, Kanazawa, Japan
3 Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
* To whom correspondence should be addressed. E-mail: a.van.waarde{at}pet.umcg.nl.
 |
Abstract |
|---|
-Receptors are strongly overexpressed in most rodent and human tumors and are proliferation markers. To evaluate the potential of a radiolabeled 1-ligand for therapy monitoring, we compared early changes of 11C-1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine (11C-SA4503) binding and 18F-FDG uptake in gliomas after in vivo chemotherapy. Methods: C6 cells (2.5 x 106) were subcutaneously injected into the right shoulder of male Wistar rats. After 7 d, the tumor volume was 0.60 ± 0.08 cm3. Animals then received either saline or doxorubicin (8 mg/kg, intraperitoneally). One control and 1 treated rat were imaged simultaneously, 24 or 48 h after treatment, under pentobarbital anesthesia. Rodents (n = 20) were scanned first with 11C-SA4503 (25 MBq, intravenously) followed more than 100 min afterward by 18F-FDG (20 MBq, intravenously), using a dedicated small-animal PET camera (60-min protocol, tumors in the field of view). Tumor homogenates were prepared and subjected to -receptor assays. The biodistribution of 18F-FDG was assessed. Results: Tumors appeared 4-5 d after inoculation and grew exponentially. No significant reduction of tumor growth was visible within 48 h after doxorubicin treatment. Both PET tracers visualized the tumors and showed reduced uptake after chemotherapy (11C-SA4503: 26.5% ± 6.5% at 24 h, 26.5% ± 7.5% at 48 h; 18F-FDG: 22.6% ± 3.2% at 24 h, 27.4% ± 3.2% at 48 h; ex vivo 18F-FDG: 22.4% ± 5.4% at 24 h, 31.7% ± 12.7% at 48 h). 1-Receptor density in treated tumors was also reduced (from 172 ± 35 to 125 ± 28 fmol/mg of protein). Conclusion: Both 11C-SA4503 binding and 18F-FDG uptake declined in gliomas after chemotherapy. Decreased binding of 11C-SA4503 corresponded to a loss of 1-receptors from the tumors. Changes in tracer uptake preceded the morphologic changes by at least 48 h.
Key Words:
11C-SA4503, chemotherapy, tumor, doxorubicin, microPET
