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Targeting murine heart and brain: visualisation conditions for multi-pinhole SPECT with (99m)Tc- and (123)I-labelled probes.

Pissarek M, Meyer-Kirchrath J, Hohlfeld T, Vollmar S, Oros-Peusquens AM, Flögel U, Jacoby C, Krügel U, Schramm N - Eur. J. Nucl. Med. Mol. Imaging (2009)

Bottom Line: Alterations of maximal cerebral uptake of [(123)I]IBZM by >20% (116 kBq) were verified with the prerequisite of 50% striatal of total uptake.The labelling with [(99m)Tc]sestamibi revealed a 30% lower uptake in cardiomyopathic hearts compared to wild types. [(123)I]IPPA uptake could be visualised at activity doses of 0.8 MBq/g body weight.The thresholds of detection for differences in the tracer uptake determined under the conditions of our experiments well reflect distinctions in molar activity and uptake characteristics of the tracers.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neurosciences and Biophysics-Nuclear Chemistry (INB-4), Research Centre Juelich, Leo-Brandt-Str., 52428, Juelich, Germany. m.pissarek@fz-juelich.de

ABSTRACT

Purpose: The study serves to optimise conditions for multi-pinhole SPECT small animal imaging of (123)I- and (99m)Tc-labelled radiopharmaceuticals with different distributions in murine heart and brain and to investigate detection and dose range thresholds for verification of differences in tracer uptake.

Methods: A Triad 88/Trionix system with three 6-pinhole collimators was used for investigation of dose requirements for imaging of the dopamine D(2) receptor ligand [(123)I]IBZM and the cerebral perfusion tracer [(99m)Tc]HMPAO (1.2-0.4 MBq/g body weight) in healthy mice. The fatty acid [(123)I]IPPA (0.94 +/- 0.05 MBq/g body weight) and the perfusion tracer [(99m)Tc]sestamibi (3.8 +/- 0.45 MBq/g body weight) were applied to cardiomyopathic mice overexpressing the prostaglandin EP(3) receptor.

Results: In vivo imaging and in vitro data revealed 45 kBq total cerebral uptake and 201 kBq cardiac uptake as thresholds for visualisation of striatal [(123)I]IBZM and of cardiac [(99m)Tc]sestamibi using 100 and 150 s acquisition time, respectively. Alterations of maximal cerebral uptake of [(123)I]IBZM by >20% (116 kBq) were verified with the prerequisite of 50% striatal of total uptake. The labelling with [(99m)Tc]sestamibi revealed a 30% lower uptake in cardiomyopathic hearts compared to wild types. [(123)I]IPPA uptake could be visualised at activity doses of 0.8 MBq/g body weight.

Conclusion: Multi-pinhole SPECT enables detection of alterations of the cerebral uptake of (123)I- and (99m)Tc-labelled tracers in an appropriate dose range in murine models targeting physiological processes in brain and heart. The thresholds of detection for differences in the tracer uptake determined under the conditions of our experiments well reflect distinctions in molar activity and uptake characteristics of the tracers.

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Time course of striatal uptake of [123I]IBZM. Uptake of [123I]IBZM is shown after application of 0.44, 0.56, 0.61 and 0.95 MBq/g body weight in mice. Imaging conditions were used as described in the legend of Fig. 2. The numbers of the x-axis correspond to the consecutive acquisition periods 1 to 8. a Time course analysed using the Vinci 2.3.1. processing tool. b Time course analysed using the InVivoScope processing tool
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Fig3: Time course of striatal uptake of [123I]IBZM. Uptake of [123I]IBZM is shown after application of 0.44, 0.56, 0.61 and 0.95 MBq/g body weight in mice. Imaging conditions were used as described in the legend of Fig. 2. The numbers of the x-axis correspond to the consecutive acquisition periods 1 to 8. a Time course analysed using the Vinci 2.3.1. processing tool. b Time course analysed using the InVivoScope processing tool

Mentions: The evaluation of uptake of [123I]IBZM by means of the Vinci 2.3.1. processing tool shown in Fig. 3a was performed using a volume-based approach as described earlier [30]. Figure 3b presents the respective data obtained by means of the InVivoScope processing tool. The proportion between specific and non-specific binding related to the total volume of the brain decreased from 1:5 to values > 1 at the 100th min of the observation period (fifth acquisition period; data not shown). A comparison of the data points obtained for the four doses (for each dose mean value of all acquisition periods with exception of period 2 and 6) using ANOVA followed by the Student-Newman-Keuls post hoc test (Fig. 4a, b) reveals the range in which the multi-pinhole system reflects differences in the uptake of the receptor ligand under the experimental condition described. Differences between the mean values obtained using the Vinci 2.3.1. processing tool were identified as significant upward from 20% of the uptake at the maximal dose activities applied. The same uptake was reflected with a 30% difference (610 kBq/g body weight and 510 kBq/g body weight obtaining group) but with the same probability of significance with the InVivoScope processing tool. Figure 5 shows good correlations between activity measurements of excised brains in vitro and the intensity values observed in vivo (Fig. 5a) analysed by means of the InVivoScope data processing tool. The border of detection is indicated by interpolation of the regression line to the x-axis (Fig. 5a) revealing 45 kBq as the smallest activity accumulated in the whole brain under in vivo conditions for appropriate visualisation of the striata following application of [123I]IBZM. The SUV calculated for all brains was SUV = 0.36 ± 0.016 giving a relative standard deviation of 9% for the [123I]IBZM experiments reflecting a variation coefficient in a range expectable for an in vivo method for the determination of physiological parameters applied to a small group of animals. InVivoScope data obtained in the striata in vivo and their correlation with the respective data points determined by means of the Vinci processing tool are shown for the third acquisition period (Fig. 5b) and for the eighth acquisition period (Fig. 5c).Fig. 3


Targeting murine heart and brain: visualisation conditions for multi-pinhole SPECT with (99m)Tc- and (123)I-labelled probes.

Pissarek M, Meyer-Kirchrath J, Hohlfeld T, Vollmar S, Oros-Peusquens AM, Flögel U, Jacoby C, Krügel U, Schramm N - Eur. J. Nucl. Med. Mol. Imaging (2009)

Time course of striatal uptake of [123I]IBZM. Uptake of [123I]IBZM is shown after application of 0.44, 0.56, 0.61 and 0.95 MBq/g body weight in mice. Imaging conditions were used as described in the legend of Fig. 2. The numbers of the x-axis correspond to the consecutive acquisition periods 1 to 8. a Time course analysed using the Vinci 2.3.1. processing tool. b Time course analysed using the InVivoScope processing tool
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2724637&req=5

Fig3: Time course of striatal uptake of [123I]IBZM. Uptake of [123I]IBZM is shown after application of 0.44, 0.56, 0.61 and 0.95 MBq/g body weight in mice. Imaging conditions were used as described in the legend of Fig. 2. The numbers of the x-axis correspond to the consecutive acquisition periods 1 to 8. a Time course analysed using the Vinci 2.3.1. processing tool. b Time course analysed using the InVivoScope processing tool
Mentions: The evaluation of uptake of [123I]IBZM by means of the Vinci 2.3.1. processing tool shown in Fig. 3a was performed using a volume-based approach as described earlier [30]. Figure 3b presents the respective data obtained by means of the InVivoScope processing tool. The proportion between specific and non-specific binding related to the total volume of the brain decreased from 1:5 to values > 1 at the 100th min of the observation period (fifth acquisition period; data not shown). A comparison of the data points obtained for the four doses (for each dose mean value of all acquisition periods with exception of period 2 and 6) using ANOVA followed by the Student-Newman-Keuls post hoc test (Fig. 4a, b) reveals the range in which the multi-pinhole system reflects differences in the uptake of the receptor ligand under the experimental condition described. Differences between the mean values obtained using the Vinci 2.3.1. processing tool were identified as significant upward from 20% of the uptake at the maximal dose activities applied. The same uptake was reflected with a 30% difference (610 kBq/g body weight and 510 kBq/g body weight obtaining group) but with the same probability of significance with the InVivoScope processing tool. Figure 5 shows good correlations between activity measurements of excised brains in vitro and the intensity values observed in vivo (Fig. 5a) analysed by means of the InVivoScope data processing tool. The border of detection is indicated by interpolation of the regression line to the x-axis (Fig. 5a) revealing 45 kBq as the smallest activity accumulated in the whole brain under in vivo conditions for appropriate visualisation of the striata following application of [123I]IBZM. The SUV calculated for all brains was SUV = 0.36 ± 0.016 giving a relative standard deviation of 9% for the [123I]IBZM experiments reflecting a variation coefficient in a range expectable for an in vivo method for the determination of physiological parameters applied to a small group of animals. InVivoScope data obtained in the striata in vivo and their correlation with the respective data points determined by means of the Vinci processing tool are shown for the third acquisition period (Fig. 5b) and for the eighth acquisition period (Fig. 5c).Fig. 3

Bottom Line: Alterations of maximal cerebral uptake of [(123)I]IBZM by >20% (116 kBq) were verified with the prerequisite of 50% striatal of total uptake.The labelling with [(99m)Tc]sestamibi revealed a 30% lower uptake in cardiomyopathic hearts compared to wild types. [(123)I]IPPA uptake could be visualised at activity doses of 0.8 MBq/g body weight.The thresholds of detection for differences in the tracer uptake determined under the conditions of our experiments well reflect distinctions in molar activity and uptake characteristics of the tracers.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neurosciences and Biophysics-Nuclear Chemistry (INB-4), Research Centre Juelich, Leo-Brandt-Str., 52428, Juelich, Germany. m.pissarek@fz-juelich.de

ABSTRACT

Purpose: The study serves to optimise conditions for multi-pinhole SPECT small animal imaging of (123)I- and (99m)Tc-labelled radiopharmaceuticals with different distributions in murine heart and brain and to investigate detection and dose range thresholds for verification of differences in tracer uptake.

Methods: A Triad 88/Trionix system with three 6-pinhole collimators was used for investigation of dose requirements for imaging of the dopamine D(2) receptor ligand [(123)I]IBZM and the cerebral perfusion tracer [(99m)Tc]HMPAO (1.2-0.4 MBq/g body weight) in healthy mice. The fatty acid [(123)I]IPPA (0.94 +/- 0.05 MBq/g body weight) and the perfusion tracer [(99m)Tc]sestamibi (3.8 +/- 0.45 MBq/g body weight) were applied to cardiomyopathic mice overexpressing the prostaglandin EP(3) receptor.

Results: In vivo imaging and in vitro data revealed 45 kBq total cerebral uptake and 201 kBq cardiac uptake as thresholds for visualisation of striatal [(123)I]IBZM and of cardiac [(99m)Tc]sestamibi using 100 and 150 s acquisition time, respectively. Alterations of maximal cerebral uptake of [(123)I]IBZM by >20% (116 kBq) were verified with the prerequisite of 50% striatal of total uptake. The labelling with [(99m)Tc]sestamibi revealed a 30% lower uptake in cardiomyopathic hearts compared to wild types. [(123)I]IPPA uptake could be visualised at activity doses of 0.8 MBq/g body weight.

Conclusion: Multi-pinhole SPECT enables detection of alterations of the cerebral uptake of (123)I- and (99m)Tc-labelled tracers in an appropriate dose range in murine models targeting physiological processes in brain and heart. The thresholds of detection for differences in the tracer uptake determined under the conditions of our experiments well reflect distinctions in molar activity and uptake characteristics of the tracers.

Show MeSH