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. One- and 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.

First-in-Humans Study of 68Ga-DOTA-Siglec-9, a PET Ligand Targeting Vascular Adhesion Protein 1

“…In addition to intact 68 Ga-DOTA-Siglec-9, several additional peaks were observed in plasma radio-HPLC chromatograms, but we did not further identify the radiometabolites of plasma or investigate their extent at the inflammatory sites. Radiometabolism and plasma protein binding are consistent with values reported previously in pigs (6,21).…”

Attempts to Target Staphylococcus aureus Induced Osteomyelitis Bone Lesions in a Juvenile Pig Model by Using Radiotracers

“…The uptake of [ 68 Ga]Ga-DOTA-Siglec-9 had reversible kinetics and could be modeled with the rev2TCM (4 k-parameters). We demonstrated that [ 68 Ga]Ga-DOTA-Siglec-9 was metabolized very quickly and no increased [ 68 Ga]Ga-DOTA-Siglec-9 uptake was seen in OM [ 13 ]. However, the distribution volume for the uptake of soft tissue infections was elevated, concluding the tracer has a role for soft tissue infections, but not for bone infections (osteomyelitis).…”

“…In the present study, we also observed an affinity of [ 68 Ga]Ga-DOTA-Siglec-9 for infected soft tissue ( Figure 7 and Figure 8 ), although the tracer was present for a short period in this infectious compartment ( Figure 8 ). We can conclude that static scanning should have been earlier when visualizing infections in soft tissues, as the tracer turned out to be reversible [ 13 ]. The reason for uptake in the lungs ( Figure 7 ) may be due to an infection, or it may be a result of tracer-trapping in the pulmonary tissue, as the whole-body biodistribution of [ 68 Ga]Ga-DOTA-Siglec-9 showed, in general, a significant uptake or accumulation in the lungs, also in non-infected lungs.…”

“…We also examined the vascular adhesion protein 1 (VAP-1)-targeted PET tracer [ 68 Ga]Ga-DOTA-Siglec-9, as an alternative to the traditional tracers for detecting infections. Sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) is a natural ligand for VAP-1 and is expressed on monocytes and neutrophils and is involved in leukocyte trafficking [13].…”

Carbon Nanomaterials for Sorption of 68Ga for Potential Using in Positron Emission Tomography

“…Among radionuclides suitable for PET, 68 Ga is one of the most promising isotopes for widespread use [ 23 , 24 , 25 ]. It has a suitable set of nuclear physical characteristics (T 1/2 = 68 min, 100% β + ) and high availability, as it can be obtained from a 68 Ge/ 68 Ga generator.…”