TY - JOUR T1 - A simplified kinetic model for rat glioma with [<sup>18</sup>F]FAHA JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1182 LP - 1182 VL - 52 IS - supplement 1 AU - Jung-Wen Kuo AU - Kuan-Hao Su AU - Chun-Yi Wu AU - Chung-Hsien Ho AU - Hsin-Ell Wang AU - Juri Gelovani AU - Ren-Shyan Liu Y1 - 2011/05/01 UR - http://jnm.snmjournals.org/content/52/supplement_1/1182.abstract N2 - 1182 Objectives [18F]-6-(fluoroacetamide)-1-hexanoicanilide ([18F]FAHA) is useful for non-invasive monitoring the activity of histone deacetylase (HDAC) in tumor and neurodegenerative disorders. The quantification of FAHA was complicated that the fitting model involves a three-tissue-five-compartment model (CM), and metabolite fraction is demanded due to a great amount of tracer was metabolized to fluoroacetate (FAC) in the periphery. This study is to find a physiological simplification relationship between the FAHA 5-CM and 3-CM for non-invasive studies. Methods F98 rat glioma cells were implanted into left forebrain of 5 Fischer rats to establish the animal tumor model. SAHA, an HDAC inhibitor, was administrated twice a day for two days (100 mg/kg). Dynamic PET imaging for 60 min with [18F]FAHA and [18F]FAC were acquired. FAHA/FAC fractions in plasma were measured using HPLC. Image-derived cardiac input functions were applied on the quantitative analysis. FAHA 5-CM with k1~k8 was used for FAHA quantification. Furthermore, the reversible 3-CM was used to estimate the FAC kinetic parameters. The response of the 5-CM of FAHA can then be simulated to evaluate the relationship between the kinetic parameters of the 5-CM and those of the 3-CM. Results k3 of the 5-CM (k3-5CM) represented the catalytic activity of HDAC. In the simulation study, k3 of the 3-CM (k3-3CM) exhibited a monotonic increasing with the k3-5CM (non-linear regression: y=0.12+0.34*(1-exp(-1.10*x)), R2=0.9998). The same phenomenon can also be observed in the results of the 3-CM flux constant (Ki). The k3-3CM was decreased from 0.37 min-1 to 0.14 min-1 after treating with SAHA. When transforming k3-3CM with the regression equation, the k3-5CM decreased from 1.20 min-1 to 0.06 min-1. Conclusions This simplified compartment model is adequate for quantitative assessment of the activity of HDAC in brain tumor using [18F]FAHA PET ER -