quantified and analyzed using compartment models to better understand the kidney
transit of free siRNA and siRNA nanoparticles. The parameters for modeling the
kinetics of free siRNA was derived from anatomical properties of the kidney and by
fitting the PET time-activity curves. The siRNA nanoparticle models were then
constructed by adding the parameters describing the GBM accumulation and disassembly and the peri-tubule endothelial uptake into the model for free siRNA. The
two models well describe the kinetics of both
64 Cu-labeled free siRNA and siRNA
nanoparticles thereby conforming the suggested underlying mechanism of rapid
renal excretion of CDP-based nanoparticles (Fig. 16.5) [55]. This improved
understanding of the clearance mechanism of CDP-based nanoparticles provides
invaluable insights to guide the design of more effective nanoparticles for siRNA
delivery.
References
1. D.S. Lee, H.-J. Im, Y.-S. Lee, Radionanomedicine: widened perspectives of molecular
theragnosis. Nanomedicine 11(4), 795–810 (2015)
2. E.C. Pratt, T.M. Shaffer, J. Grimm, Nanoparticles and radiotracers: advances toward
radionanomedicine. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 8(6), 872–890 (2016)
3. R.E. Carson, Tracer kinetic modeling in PET, in Positron Emission Tomography (Springer,
Berlin, 2005), pp. 127–159
4. A. Gjedde, W.R. Bauer, D. Wong, Neurokinetics: The Dynamics of Neurobiology In Vivo
(Springer Science & Business Media, Berlin. 2010)
5. J.S. Lee, D.S. Lee, Tracer kinetic analysis for PET and SPECT. Med. Imaging Technol. Appl.
201(3) (2013)
6. S.R. Cherry, J. Sorenson, M.E. Phelps, B.M. Methé, Physics in nuclear medicine. Med. Phys.
31(8), 2370–2371 (2004)
7. E. Kim, O.D. Howes, B.-H. Kim, M.-W. Chon, S. Seo, F.E. Turkheimer et al., Regional
differences in serotonin transporter occupancy by escitalopram: an [
11
C] DASB PK-PD study.
Clin. Pharmacokinet. 56(4), 371–381 (2017)
8. J.S. Lee, D.S. Lee, Analysis of functional brain images using population-based probabilistic
atlas. Curr. Med. Imaging Rev. 1(1), 81–87 (2005)
9. J.-Y. Lee, S.H. Seo, Y.K. Kim, H.B. Yoo, Y.E. Kim, I.C. Song et al., Extrastriatal
dopaminergic changes in Parkinson’s disease patients with impulse control disorders.
J. Neurol. Neurosurg. Psychiatry (2013)
10. Y. Choi, R.A. Hawkins, S.-C. Huang, S.S. Gambhir, R.C. Brunken, M.E. Phelps et al.,
Parametric images of myocardial metabolic rate of glucose generated from dynamic cardiac
PET and 2-[
18
F] fluoro-2-deoxy-d-glucose studies. J. Nucl. Med. 32(4), 733–738 (1991)
11. R.N. Gunn, A.A. Lammertsma, S.P. Hume, V.J. Cunningham, Parametric imaging of
ligand-receptor binding in PET using a simplified reference region model. Neuroimage 6(4),
279–287 (1997)
12. J.S. Lee, D.S. Lee, J.Y. Ahn, J.S. Yeo, G.J. Cheon, S.-K. Kim et al., Generation of parametric
image of regional myocardial blood flow using H 2
15
O dynamic PET and a linear least-squares
method. J. Nucl. Med. 46(10), 1687–1695 (2005)
13. S. Seo, S.J. Kim, Y.K. Kim, J.-Y. Lee, J.M. Jeong, D.S. Lee et al., Comparative assessment of
parametric neuroreceptor mapping approaches based on the simplified reference tissue model
using [
11
C] ABP688 PET. J. Cereb. Blood Flow Metab. 35(12), 2098–2108 (2015)
16 Tracer Kinetics in Radionanomedicine
307
transit of free siRNA and siRNA nanoparticles. The parameters for modeling the
kinetics of free siRNA was derived from anatomical properties of the kidney and by
fitting the PET time-activity curves. The siRNA nanoparticle models were then
constructed by adding the parameters describing the GBM accumulation and disassembly and the peri-tubule endothelial uptake into the model for free siRNA. The
two models well describe the kinetics of both
64 Cu-labeled free siRNA and siRNA
nanoparticles thereby conforming the suggested underlying mechanism of rapid
renal excretion of CDP-based nanoparticles (Fig. 16.5) [55]. This improved
understanding of the clearance mechanism of CDP-based nanoparticles provides
invaluable insights to guide the design of more effective nanoparticles for siRNA
delivery.
References
1. D.S. Lee, H.-J. Im, Y.-S. Lee, Radionanomedicine: widened perspectives of molecular
theragnosis. Nanomedicine 11(4), 795–810 (2015)
2. E.C. Pratt, T.M. Shaffer, J. Grimm, Nanoparticles and radiotracers: advances toward
radionanomedicine. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 8(6), 872–890 (2016)
3. R.E. Carson, Tracer kinetic modeling in PET, in Positron Emission Tomography (Springer,
Berlin, 2005), pp. 127–159
4. A. Gjedde, W.R. Bauer, D. Wong, Neurokinetics: The Dynamics of Neurobiology In Vivo
(Springer Science & Business Media, Berlin. 2010)
5. J.S. Lee, D.S. Lee, Tracer kinetic analysis for PET and SPECT. Med. Imaging Technol. Appl.
201(3) (2013)
6. S.R. Cherry, J. Sorenson, M.E. Phelps, B.M. Methé, Physics in nuclear medicine. Med. Phys.
31(8), 2370–2371 (2004)
7. E. Kim, O.D. Howes, B.-H. Kim, M.-W. Chon, S. Seo, F.E. Turkheimer et al., Regional
differences in serotonin transporter occupancy by escitalopram: an [
11
C] DASB PK-PD study.
Clin. Pharmacokinet. 56(4), 371–381 (2017)
8. J.S. Lee, D.S. Lee, Analysis of functional brain images using population-based probabilistic
atlas. Curr. Med. Imaging Rev. 1(1), 81–87 (2005)
9. J.-Y. Lee, S.H. Seo, Y.K. Kim, H.B. Yoo, Y.E. Kim, I.C. Song et al., Extrastriatal
dopaminergic changes in Parkinson’s disease patients with impulse control disorders.
J. Neurol. Neurosurg. Psychiatry (2013)
10. Y. Choi, R.A. Hawkins, S.-C. Huang, S.S. Gambhir, R.C. Brunken, M.E. Phelps et al.,
Parametric images of myocardial metabolic rate of glucose generated from dynamic cardiac
PET and 2-[
18
F] fluoro-2-deoxy-d-glucose studies. J. Nucl. Med. 32(4), 733–738 (1991)
11. R.N. Gunn, A.A. Lammertsma, S.P. Hume, V.J. Cunningham, Parametric imaging of
ligand-receptor binding in PET using a simplified reference region model. Neuroimage 6(4),
279–287 (1997)
12. J.S. Lee, D.S. Lee, J.Y. Ahn, J.S. Yeo, G.J. Cheon, S.-K. Kim et al., Generation of parametric
image of regional myocardial blood flow using H 2
15
O dynamic PET and a linear least-squares
method. J. Nucl. Med. 46(10), 1687–1695 (2005)
13. S. Seo, S.J. Kim, Y.K. Kim, J.-Y. Lee, J.M. Jeong, D.S. Lee et al., Comparative assessment of
parametric neuroreceptor mapping approaches based on the simplified reference tissue model
using [
11
C] ABP688 PET. J. Cereb. Blood Flow Metab. 35(12), 2098–2108 (2015)
16 Tracer Kinetics in Radionanomedicine
307