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

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 -