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Background: In order to acquire accurate drug pharmacokinetic information, which is required for tissue dosimetry, micro-SPECT must be quantitative to allow for an accurate assessment of radioligand activity in the relevant tissue. This study investigates the feasibility of deriving accurate mouse-specific time-integrated drug pharmacokinetic data in mouse kidneys from activity measurements using micro-SPECT. Methods: An animal experiment was carried out to evaluate the accuracy of 131I activity quantification in mouse kidneys (mean tissue volume of 0.140 mL) using a micro-SPECT system against conventional ex vivo gamma counting (GC) in a NaI(Tl) detector. The imaging setting investigated was that of the mouse biodistribution of a 131I-labelled single-domain antibody fragment (sdAb), currently being investigated for targeted radionuclide therapy of HER2-expressing cancer. SPECT imaging of 131I 365-keV photons was done with a VECTor/CT system (MILabs, Netherlands) using a high-energy mouse collimator with 1.6-mm-diameter pinholes. For both activity quantification techniques, the pharmacokinetic profile of the radioligand from approximately 1–73 h p.i. was derived and the time-integrated activity coefficient per gram of tissue (ã/M) was estimated. Additionally, SPECT activity recovery coefficients were determined in a phantom setting. Results: SPECT activities underestimate the reference activities by an amount that is dependent on the 131I activity concentration in the kidney, and thus on the time point of the pharmacokinetic profile. This underestimation is around − 12% at 1.5 h (2.89 MBq mL−1 mean reference activity concentration), − 13% at 6.6 h (149 kBq mL−1), − 40% at 24 h (17.6 kBq mL−1) and − 46% at 73 h (5.2 kBq mL−1) p.i. The ã/M value estimated from SPECT activities is, nevertheless, within − 14% from the reference (GC) ã/M value. Furthermore, better quantitative accuracy (within 2% from GC) in the SPECT ã/M value is achieved when SPECT activities are compensated for partial recovery with a phantom-based recovery coefficient of 0.85. Conclusion: The SPECT imaging system used, together with a robust activity quantification methodology, allows an accurate estimation of time-integrated pharmacokinetic information of the 131I-labelled sdAb in mouse kidneys. This opens the possibility to perform mouse-specific kidney-tissue dosimetry based on pharmacokinetic data acquired in vivo on the same mice used in nephrotoxicity studies. [ABSTRACT FROM AUTHOR]

Background: A multicenter intercomparison assessment was made of the variation in left ventricular (LV) volumes and ejection fractions (EFs) obtained from gated myocardial perfusion single photon emission computed tomography (SPECT) of the 3-dimensional AGATE (Amsterdam gated) cardiac phantom.Methods and Results: The phantom was configured to produce 3 different standard end-systolic volume and end-diastolic volume combinations (50 mL and 120 mL, 90 mL and 160 mL, and 120 mL and 190 mL) with corresponding EF (58%, 44%, and 37%). Quantitative gated myocardial perfusion SPECT was performed with 39 SPECT systems in 35 departments. In the multicenter study, for all 3 filling conditions, a wide range of results was obtained. The EF was overestimated (by 1% to 15%), and both the end-systolic volume and end-diastolic volume were underestimated (by 1 to 65 mL). The extent of overestimation of EF was related to the extent of underestimation of the volumes and was independent of filling condition. The trend in error per center was comparable for all 3 filling conditions. Acquisition time per projection was the only independent predictor of the difference between measured and expected EF (P = .0001).Conclusions: Care should be taken before extrapolation of published and accepted cutoff values for LV EF and volumes in clinical decision making. Results should be validated in each center and monitored for accuracy and consistency over time. [ABSTRACT FROM AUTHOR]

Background: Although several myocardial iodine 123 metaiodobenzylguanidine (MIBG) indices are increasingly used to detect alterations in myocardial sympathetic activity in various forms of cardiac pathology, published measurements of normal values and within-subject variability are lacking.Methods and Results: Twenty-five healthy volunteers underwent planar and single photon emission computed tomography (SPECT) imaging. Heart-mediastinum ratio (H/M) and myocardial washout were calculated from planar images comparing three different methods for the assessment of myocardial activity: (1) global region over the myocardium (cavity included), (2) global region over the myocardium (cavity excluded), and (3) fixed small myocardial region. Segmental (relative) uptake and washout were assessed by SPECT. For all MIBG indices, the interindividual variation was the lowest for methods 1 and 2. In SPECT this variation was low for relative segmental uptake compared with washout. In 9 subjects a second MIBG scintigraphy was performed after 3 months. The within-subject variability of H/M and washout assessed by planar methods 1 and 2 was 5%, whereas it was approximately 9% for planar method 3. For relative segmental uptake from SPECT, this variability was 5%.Conclusion: MIBG H/M (planar) and relative segmental uptake (SPECT) show a low interindividual and within-subject variability. This enables the detection of small (regional) variations in myocardial sympathetic nervous function, especially to monitor the effect of therapeutic interventions in patients with various cardiac diseases. [ABSTRACT FROM AUTHOR]