Development of reference tissue method for multiple injections of [C-11]raclopride

Hiroshi Watabe, Youichiro Ohta, Noboru Teramoto, Yoshinori Miyake, Maki Kurokawa, Akihide Yamamoto, Yasuyuki Ose, Yoko Ikoma, Takuya Hayashi, Hidehiro Iida

Research output: Contribution to journalArticlepeer-review


Introduction: PET with [C-11]raclopride is often used to investigate D2-dopamine receptor system in brain. Temporal changes of the binding potential (BP) of [C-11]raclopride due to the internal synaptic neurotransmitter release has been attempted to measure using bolus-followed by infusion (B/I) method or simplified reference tissue (SRT) method. B/I method is attractive, as its simple mathematical formulation, but requires relatively long study period, particularly when one intends to apply it at multiple activated conditions. SRT method can be completed within a relatively short period, but still needs to be carried out independently at each of multiple [C-11]raclopride PET scans. The aim of this study is to develop reference tissue method to estimate multiple BP values from a single session of PET scanning in conjunction with multiple injections of [C-11]raclopride. Methods: The second [C-11]raclopride will be injected followed by the first injection of [C-11]raclopride after certain period. In order to estimate BP after the second injection, SRT method is extended to consider the residual radioactivity from the first injection of [C-11]raclopride. In order to validate the method, we performed rodent studies (n=4, Wister rat male, 8-10 weeks old, 203 - 334 g) with PET and [C-11]raclopride. Rats were anesthetize by propofol and 37MBq of [C-11]raclopride (specific radioactivity of 8.2 - 34 GBq/umol) was injected and simultaneously PET acquisition was started. PET camera was MicroPET focus 120(Siemens). After 20 minutes of the injection of [C-11]raclopride, 37 MBq of [C-11]raclopride (specific radioactivity of 1.1 - 6.0 GBq/umol) diluted by cold raclopride was injected. PET data was acquired as list mode data and histogramed to the multiple sinogram data with 2 minutes time interval. All sinogram data were reconstructed by 2D filtered backprojection after Fourier rebinning technique. Regions of interest were placed on regions of basal ganglia and cerebellum and time activity curves were generated. Computer simulation was also performed to evaluate the present method. Results and Discussion: Time activities curves were well fitted to the proposed model. BP values were significantly different between the 1st and 2nd injection of [C-11]raclopride attributed to the difference of the specific activity. Figure shows the relationship between mass of injected raclopride and BP value measured by the present method. Computer simulation (solid line in the figure) could well reproduce the Results: of the experiments, which suggests the feasibility of the proposed method. This technique can also easily be extended to more than three multiple jections of tracer. Conclusion: The proposed method has potential to shorten study period of several neurotransmitter competition studies.

Original languageEnglish
Pages (from-to)PP06-02U
JournalJournal of Cerebral Blood Flow and Metabolism
Issue numberSUPPL. 1
Publication statusPublished - 2007 Nov 13


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