Multi-organ Kinetic Modeling for Na[F]F Pre-clinical Total-body PET Studies

Overview

Journal Med Phys

Specialty Biophysics

Date 2024 Nov 5

PMID 39499788

Authors

Jose Benitez-Aurioles

Paul S Clegg

Carlos J Alcaide-Corral

Catriona Wimberley

Adriana A S Tavares

Affiliations

Soon will be listed here.

Abstract

Background: Total-body positron emission tomography (PET), already well-established in the pre-clinical setting, makes it possible to study multi-parameters in biological systems as a whole, rather than focusing on single tissues analysis. Simultaneous kinetic analysis of multiple organs poses some daunting new challenges.

Purpose: To explore quantifying the pharmacokinetics of Na[F]F in multiple dissimilar murine organs simultaneously in vivo with total-body PET imaging using different compartmental models for each organ and a shared cardiovascular system.

Methods: Six mice underwent a 60-min total-body PET scan following intravenous bolus injection of Na[F]F. Compartmental models were constructed for each organ (heart, lungs, liver, kidneys, and bone) using an image derived input function. Non-linear least squares fitting of a model that connects the five organs to a shared cardiovascular system was used to analyze both the first 3 min of data and the full hour. Analysis was repeated 5000 times using different initial parameter values for each duration, permitting analysis of correlations between parameters.

Results: The models give a good qualitative account of the activity curves irrespective of the duration of the data; however, the quality of the fits to 3 min of data (average is 2.72) was generally better. Comparison of perfusion values to literature values was possible for the liver and lungs with the former (liver, 0.540 ± 0.177 mL/ml/min) being well-above expectations and the latter (lungs, 0.184 ± 0.413 mL/ml/min) in rough agreement. Correlations between microparameter values (especially affecting k) caused very noticeable problems for data modeling from both the kidneys and the femur.

Conclusion: The present study demonstrates an approach to performing kinetic modeling for multiple organs simultaneously with Na[F]F. The observed correlations between microparameter values remain a challenge. Nonetheless, many microparameters can be estimated reliably with a quantitative analysis of perfusion being possible for some organs.

Citing Articles

Multi-organ kinetic modeling for Na[F]F pre-clinical total-body PET studies.

Benitez-Aurioles J, Clegg P, Alcaide-Corral C, Wimberley C, Tavares A Med Phys. 2024; 52(2):924-937.

PMID: 39499788 PMC: 11788250. DOI: 10.1002/mp.17499.

References

Mankoff D, Shields A, Link J, Graham M, Muzi M, Peterson L . Kinetic analysis of 2-[11C]thymidine PET imaging studies: validation studies. J Nucl Med. 1999; 40(4):614-24. View

Feng T, Zhao Y, Shi H, Li H, Zhang X, Wang G . Total-Body Quantitative Parametric Imaging of Early Kinetics of F-FDG. J Nucl Med. 2020; 62(5):738-744. PMC: 8844261. DOI: 10.2967/jnumed.119.238113. View

Liu G, Yu H, Shi D, Hu P, Hu Y, Tan H . Short-time total-body dynamic PET imaging performance in quantifying the kinetic metrics of F-FDG in healthy volunteers. Eur J Nucl Med Mol Imaging. 2021; 49(8):2493-2503. DOI: 10.1007/s00259-021-05500-2. View

Hildebrandt I, Su H, Weber W . Anesthesia and other considerations for in vivo imaging of small animals. ILAR J. 2008; 49(1):17-26. DOI: 10.1093/ilar.49.1.17. View

Logan J, Fowler J, Volkow N, Ding Y, Wang G, Alexoff D . A strategy for removing the bias in the graphical analysis method. J Cereb Blood Flow Metab. 2001; 21(3):307-20. DOI: 10.1097/00004647-200103000-00014. View

Beheshti M, Rezaee A, Geinitz H, Loidl W, Pirich C, Langsteger W . Evaluation of Prostate Cancer Bone Metastases with 18F-NaF and 18F-Fluorocholine PET/CT. J Nucl Med. 2016; 57(Suppl 3):55S-60S. DOI: 10.2967/jnumed.115.169730. View

Thorn S, deKemp R, Dumouchel T, Klein R, Renaud J, Wells R . Repeatable noninvasive measurement of mouse myocardial glucose uptake with 18F-FDG: evaluation of tracer kinetics in a type 1 diabetes model. J Nucl Med. 2013; 54(9):1637-44. DOI: 10.2967/jnumed.112.110114. View

Viswanath V, Sari H, Pantel A, Conti M, Daube-Witherspoon M, Mingels C . Abbreviated scan protocols to capture F-FDG kinetics for long axial FOV PET scanners. Eur J Nucl Med Mol Imaging. 2022; 49(9):3215-3225. PMC: 10695012. DOI: 10.1007/s00259-022-05747-3. View

Wu Y, Feng T, Zhao Y, Xu T, Fu F, Huang Z . Whole-Body Parametric Imaging of F-FDG PET Using uEXPLORER with Reduced Scanning Time. J Nucl Med. 2021; 63(4):622-628. PMC: 8973287. DOI: 10.2967/jnumed.120.261651. View

10.

Leithner C, Muller S, Fuchtemeier M, Lindauer U, Dirnagl U, Royl G . Determination of the brain-blood partition coefficient for water in mice using MRI. J Cereb Blood Flow Metab. 2010; 30(11):1821-4. PMC: 3023928. DOI: 10.1038/jcbfm.2010.160. View

11.

Feng D, Huang S, Wang X . Models for computer simulation studies of input functions for tracer kinetic modeling with positron emission tomography. Int J Biomed Comput. 1993; 32(2):95-110. DOI: 10.1016/0020-7101(93)90049-c. View

12.

DURBIN P, JEUNG N, Kullgren B, Clemons G . Gross composition and plasma and extracellular water volumes of tissues of a reference mouse. Health Phys. 1992; 63(4):427-42. DOI: 10.1097/00004032-199210000-00007. View

13.

Wang G, Nardo L, Parikh M, Abdelhafez Y, Li E, Spencer B . Total-Body PET Multiparametric Imaging of Cancer Using a Voxelwise Strategy of Compartmental Modeling. J Nucl Med. 2021; 63(8):1274-1281. PMC: 9364337. DOI: 10.2967/jnumed.121.262668. View

14.

Zaker N, Kotasidis F, Garibotto V, Zaidi H . Assessment of Lesion Detectability in Dynamic Whole-Body PET Imaging Using Compartmental and Patlak Parametric Mapping. Clin Nucl Med. 2020; 45(5):e221-e231. DOI: 10.1097/RLU.0000000000002954. View

15.

Carabotti M, Scirocco A, Maselli M, Severi C . The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol. 2015; 28(2):203-209. PMC: 4367209. View

16.

Moses W . Fundamental Limits of Spatial Resolution in PET. Nucl Instrum Methods Phys Res A. 2011; 648 Supplement 1:S236-S240. PMC: 3144741. DOI: 10.1016/j.nima.2010.11.092. View

17.

Benitez-Aurioles J, Clegg P, Alcaide-Corral C, Wimberley C, Tavares A . Multi-organ kinetic modeling for Na[F]F pre-clinical total-body PET studies. Med Phys. 2024; 52(2):924-937. PMC: 11788250. DOI: 10.1002/mp.17499. View

18.

MacAskill M, Stadulyte A, Williams L, Morgan T, Sloan N, Alcaide-Corral C . Quantification of Macrophage-Driven Inflammation During Myocardial Infarction with F-LW223, a Novel TSPO Radiotracer with Binding Independent of the rs6971 Human Polymorphism. J Nucl Med. 2020; 62(4):536-544. PMC: 8049364. DOI: 10.2967/jnumed.120.243600. View

19.

Piert M, Machulla H, Jahn M, Stahlschmidt A, Becker G, Zittel T . Coupling of porcine bone blood flow and metabolism in high-turnover bone disease measured by [(15)O]H(2)O and [(18)F]fluoride ion positron emission tomography. Eur J Nucl Med Mol Imaging. 2002; 29(7):907-14. DOI: 10.1007/s00259-002-0797-2. View

20.

Moller S, Bernardi M . Interactions of the heart and the liver. Eur Heart J. 2013; 34(36):2804-11. DOI: 10.1093/eurheartj/eht246. View