Comparison of 125I-BMIPP-SPECT/CT to 18F-FDG-PET/CT for imaging brown fat in a preclinical model

48 Objectives: Energy consuming and adipokine producing brown adipose tissue (BAT) is a possible anti-obesity drug target. Over 20 active and/or recruiting clinical trials registered on Clinicaltrials.gov use 18F-FDG-PET to assess BAT activity. However, 18F-FDG-PET has known poor sensitivity for BAT presence and BAT’s primary energy source is lipid. We performed SPECT/CT of BAT with 125I-BMIPP to compare results to 18F-FDG-PET/CT in mice. 123I-BMIPP is a fatty acid analogue used for cardiac imaging, particularly in Japan. Methods: A total of ten BALB/c mice (aged eight weeks, all male) were used in this study. Male mice were used as BAT activity varies throughout the estrous cycle. They were given normal chow and housed at ambient temperature during the study. Five were treated with 1 mg/kg of the BAT-activating β3-agonist CL-316,243 daily via intraperitoneal injection, and five given saline injections. 18F-FDG-PET/CT was performed on day 7 and 125I-BMIPP-SPECT/CT on day 8. 125I-BMIPP was prepared by a previously described method [1] and 18F-FDG was purchased from a commercial radiopharmacy. Thin layer chromatography demonstrated 125I-BMIPP purity >90% before each use. Mice fasted overnight before scans. They were anesthetized with isoflurane and given 3.7 MBq 18F-FDG or 14 MBq of 125I-BMIPP via the lateral tail vein. After a one-hour uptake period, mice were re-anesthetized for PET/CT or SPECT/CT. Using CT guidance, small circular regions of interest were drawn in interscapular, inguinal, and gonadal fat depots. Visual inspection of perivertebral, perirenal, anterior subcutaneous, and periesophageal fat pads was performed on all scans. 125I-BMIPP distribution in fat pads was confirmed by autoradiography in five mice. Impact of BAT activation on percent body fat (%BF) was assessed by dual energy X-ray absorptiometry in five mice. All mice were weighed at the beginning and end of the study. Means were compared with t-tests and correlations between continuous variables with Pearson’s r. Results: %BF was less in treated mice after the study period (12.9±1.9% vs 18.9±0.8%, p=0.03) but not before (p=0.55). Weight did not differ between groups before (p=0.7) or after (p=0.3) the study period.FDG mean standardized uptake value (SUVmean) was greater in interscapular, inguinal, and gonadal fat depots (primary sites of baseline BAT activity, β3-induced BAT activity, and poorly inducible BAT, respectively) in CL-316,243 treated mice compared to controls. BMIPP SUVmean was greater in interscapular and inguinal BAT in treated mice compared to controls. Detailed results are in Table 1 and representative scans in Figure 1. FDG SUVmean was correlated with BMIPP SUVmean in classical BAT (r=0.82, p=0.01) and inguinal fat (r=0.80, p=0.01), but not in gonadal fat (r=0.27, p=0.45). 18F-FDG-PET/CT and 125I-BMIPP-SPECT/CT showed activity in a similar number of mice in the perivertebral (6/10 and 5/10, respectively) and perirenal (4/10 and 5/10) fat pads. There was abdominal anterior subcutaneous activity on 125I-BMIPP-SPECT/CT in three mice compared to one mouse on 18F-FDG-PET/CT. Two animals had periesophageal uptake on 125I-BMIPP-SPECT/CT and none on 18F-FDG-PET/CT. Autoradiography after 125I-BMIPP injection confirmed greater activity in CL-316,243 treated animals compared to controls in interscapular BAT (p=0.04) and trends towards greater activity in inguinal (p=0.25) and gonadal (p=0.22) fat. Conclusions: BMIPP-SPECT/CT is a promising modality for BAT imaging. It has similar findings to 18F-FDG-PET/CT in interscapular BAT and inducible inguinal BAT in mice. There was more frequent marked BMIPP uptake than FDG uptake with CL-316,243 treatment in the anterior subcutaneous fat pad, which may be a better model than classical BAT of white adipose tissue converting to a brown phenotype that occurs in humans. Research Support: This study was supported by discretionary funds and OKO receives support from the American Diabetes Association: I-17-ICTS-05.