Kinetic modelling of [68Ga]Ga-DOTA-siglec-9 in porcine osteomyelitis and soft tissue infections

Lars Jødal; Anne Roivainen; Vesa Oikonen; Sirpa Jalkanen; Søren B. Hansen; Pia Afzelius; Aage K.O. Alstrup; Ole L. Nielsen; Svend B. Jensen

doi:10.3390/molecules24224094

Kinetic modelling of [⁶⁸Ga]Ga-DOTA-siglec-9 in porcine osteomyelitis and soft tissue infections

Lars Jødal^*, Anne Roivainen, Vesa Oikonen, Sirpa Jalkanen, Søren B. Hansen, Pia Afzelius, Aage K.O. Alstrup, Ole L. Nielsen, Svend B. Jensen

^*Corresponding author for this work

4 Citations (Scopus)

2 Downloads (Pure)

Abstract

Background: [⁶⁸Ga]Ga-DOTA-Siglec-9 is a positron emission tomography (PET) radioligand for vascular adhesion protein 1 (VAP-1), a protein involved in leukocyte trafficking. The tracer facilitates the imaging of inflammation and infection. Here, we studied the pharmacokinetic modelling of [⁶⁸Ga]Ga-DOTA-Siglec-9 in osteomyelitis and soft tissue infections in pigs. Methods: Eight pigs with osteomyelitis and soft tissue infections in the right hind limb were dynamically PET scanned for 60 min along with arterial blood sampling. The fraction of radioactivity in the blood accounted for by the parent tracer was evaluated with radio-high-performance liquid chromatography. Oneand two-tissue compartment models were used for pharmacokinetic evaluation. Post-mortem soft tissue samples from one pig were analysed with anti-VAP-1 immunofluorescence. In each analysis, the animal's non-infected left hind limb was used as a control. Results: Tracer uptake was elevated in soft tissue infections but remained low in osteomyelitis. The kinetics of [⁶⁸Ga]Ga-DOTA-Siglec-9 followed a reversible 2-tissue compartment model. The tracer metabolized quickly; however, taking this into account, produced more ambiguous results. Infected soft tissue samples showed endothelial cell surface expression of the Siglec-9 receptor VAP-1. Conclusion: The kinetics of [⁶⁸Ga]Ga-DOTA-Siglec-9 uptake in porcine soft tissue infections are best described by the 2-tissue compartment model.

Original language	English
Article number	4094
Journal	Molecules
Volume	24
Issue number	22
Number of pages	21
ISSN	1420-3049
DOIs	https://doi.org/10.3390/molecules24224094
Publication status	Published - 2019

Keywords

Animal model
Gallium-68
Infection
Inflammation
Kinetic analysis
Osteomyelitis
Siglec-9
Staphylococcus aureus
VAP-1
Vascular adhesion protein

Access to Document

10.3390/molecules24224094Licence: CC BY

Kinetic Modelling of [68Ga]Ga-DOTA-Siglec-9 in Porcine Osteomyelitis and Soft Tissue InfectionsFinal published version, 7.06 MBLicence: CC BY

Cite this

@article{04f84067de37495ab638adf43397b147,

title = "Kinetic modelling of [68Ga]Ga-DOTA-siglec-9 in porcine osteomyelitis and soft tissue infections",

abstract = "Background: [68Ga]Ga-DOTA-Siglec-9 is a positron emission tomography (PET) radioligand for vascular adhesion protein 1 (VAP-1), a protein involved in leukocyte trafficking. The tracer facilitates the imaging of inflammation and infection. Here, we studied the pharmacokinetic modelling of [68Ga]Ga-DOTA-Siglec-9 in osteomyelitis and soft tissue infections in pigs. Methods: Eight pigs with osteomyelitis and soft tissue infections in the right hind limb were dynamically PET scanned for 60 min along with arterial blood sampling. The fraction of radioactivity in the blood accounted for by the parent tracer was evaluated with radio-high-performance liquid chromatography. Oneand two-tissue compartment models were used for pharmacokinetic evaluation. Post-mortem soft tissue samples from one pig were analysed with anti-VAP-1 immunofluorescence. In each analysis, the animal's non-infected left hind limb was used as a control. Results: Tracer uptake was elevated in soft tissue infections but remained low in osteomyelitis. The kinetics of [68Ga]Ga-DOTA-Siglec-9 followed a reversible 2-tissue compartment model. The tracer metabolized quickly; however, taking this into account, produced more ambiguous results. Infected soft tissue samples showed endothelial cell surface expression of the Siglec-9 receptor VAP-1. Conclusion: The kinetics of [68Ga]Ga-DOTA-Siglec-9 uptake in porcine soft tissue infections are best described by the 2-tissue compartment model.",

keywords = "Animal model, Gallium-68, Infection, Inflammation, Kinetic analysis, Osteomyelitis, Siglec-9, Staphylococcus aureus, VAP-1, Vascular adhesion protein",

author = "Lars J{\o}dal and Anne Roivainen and Vesa Oikonen and Sirpa Jalkanen and Hansen, {S{\o}ren B.} and Pia Afzelius and Alstrup, {Aage K.O.} and Nielsen, {Ole L.} and Jensen, {Svend B.}",

year = "2019",

doi = "10.3390/molecules24224094",

language = "English",

volume = "24",

journal = "Molecules",

issn = "1420-3049",

publisher = "M D P I AG",

number = "22",

}

TY - JOUR

T1 - Kinetic modelling of [68Ga]Ga-DOTA-siglec-9 in porcine osteomyelitis and soft tissue infections

AU - Jødal, Lars

AU - Roivainen, Anne

AU - Oikonen, Vesa

AU - Jalkanen, Sirpa

AU - Hansen, Søren B.

AU - Afzelius, Pia

AU - Alstrup, Aage K.O.

AU - Nielsen, Ole L.

AU - Jensen, Svend B.

PY - 2019

Y1 - 2019

N2 - Background: [68Ga]Ga-DOTA-Siglec-9 is a positron emission tomography (PET) radioligand for vascular adhesion protein 1 (VAP-1), a protein involved in leukocyte trafficking. The tracer facilitates the imaging of inflammation and infection. Here, we studied the pharmacokinetic modelling of [68Ga]Ga-DOTA-Siglec-9 in osteomyelitis and soft tissue infections in pigs. Methods: Eight pigs with osteomyelitis and soft tissue infections in the right hind limb were dynamically PET scanned for 60 min along with arterial blood sampling. The fraction of radioactivity in the blood accounted for by the parent tracer was evaluated with radio-high-performance liquid chromatography. Oneand two-tissue compartment models were used for pharmacokinetic evaluation. Post-mortem soft tissue samples from one pig were analysed with anti-VAP-1 immunofluorescence. In each analysis, the animal's non-infected left hind limb was used as a control. Results: Tracer uptake was elevated in soft tissue infections but remained low in osteomyelitis. The kinetics of [68Ga]Ga-DOTA-Siglec-9 followed a reversible 2-tissue compartment model. The tracer metabolized quickly; however, taking this into account, produced more ambiguous results. Infected soft tissue samples showed endothelial cell surface expression of the Siglec-9 receptor VAP-1. Conclusion: The kinetics of [68Ga]Ga-DOTA-Siglec-9 uptake in porcine soft tissue infections are best described by the 2-tissue compartment model.

AB - Background: [68Ga]Ga-DOTA-Siglec-9 is a positron emission tomography (PET) radioligand for vascular adhesion protein 1 (VAP-1), a protein involved in leukocyte trafficking. The tracer facilitates the imaging of inflammation and infection. Here, we studied the pharmacokinetic modelling of [68Ga]Ga-DOTA-Siglec-9 in osteomyelitis and soft tissue infections in pigs. Methods: Eight pigs with osteomyelitis and soft tissue infections in the right hind limb were dynamically PET scanned for 60 min along with arterial blood sampling. The fraction of radioactivity in the blood accounted for by the parent tracer was evaluated with radio-high-performance liquid chromatography. Oneand two-tissue compartment models were used for pharmacokinetic evaluation. Post-mortem soft tissue samples from one pig were analysed with anti-VAP-1 immunofluorescence. In each analysis, the animal's non-infected left hind limb was used as a control. Results: Tracer uptake was elevated in soft tissue infections but remained low in osteomyelitis. The kinetics of [68Ga]Ga-DOTA-Siglec-9 followed a reversible 2-tissue compartment model. The tracer metabolized quickly; however, taking this into account, produced more ambiguous results. Infected soft tissue samples showed endothelial cell surface expression of the Siglec-9 receptor VAP-1. Conclusion: The kinetics of [68Ga]Ga-DOTA-Siglec-9 uptake in porcine soft tissue infections are best described by the 2-tissue compartment model.

KW - Animal model

KW - Gallium-68

KW - Infection

KW - Inflammation

KW - Kinetic analysis

KW - Osteomyelitis

KW - Siglec-9

KW - Staphylococcus aureus

KW - VAP-1

KW - Vascular adhesion protein

U2 - 10.3390/molecules24224094

DO - 10.3390/molecules24224094

M3 - Journal article

C2 - 31766140

AN - SCOPUS:85075018262

SN - 1420-3049

VL - 24

JO - Molecules

JF - Molecules

IS - 22

M1 - 4094

ER -