Pretargeted PET Imaging with a TCO-Conjugated Anti-CD44v6 Chimeric mAb U36 and [Zr]Zr-DFO-PEG-Tz.

The recent advances in the production of engineered antibodies have facilitated the development and application of tailored, target-specific antibodies. Positron emission tomography (PET) of these antibody-based drug candidates can help to better understand their behavior. In this study, we report an proof-of-concept pretargeted immuno-PET study where we compare a pretargeting vs targeted approach using a new Zr-labeled tetrazine as a bio-orthogonal ligand in an inverse electron demand Diels-Alder (IEDDA) click reaction.

Performance of nanoScan PET/CT and PET/MR for quantitative imaging of F and Zr as compared with ex vivo biodistribution in tumor-bearing mice.

Introduction: The assessment of ex vivo biodistribution is the preferred method for quantification of radiotracers biodistribution in preclinical models, but is not in line with current ethics on animal research. PET imaging allows for noninvasive longitudinal evaluation of tracer distribution in the same animals, but systemic comparison with ex vivo biodistribution is lacking. Our aim was to evaluate the potential of preclinical PET imaging for accurate tracer quantification, especially in tumor models.

PET imaging of P2XR in the experimental autoimmune encephalomyelitis model of multiple sclerosis using [C]SMW139.

Background: Non-invasive imaging of the activation status of microglia and the ability to identify a pro- or anti-inflammatory environment can provide valuable insights not only into pathogenesis of neuro-inflammatory and neurodegenerative diseases but also the monitoring of the efficacy of immunomodulatory therapies. P2XR is highly expressed on pro-inflammatory microglia and [C]SMW139, a specific P2XR tracer for positron emission tomography imaging, showed good pharmacokinetics, stability, and brain permeability in vivo. Our objective was to evaluate the potential of [C]SMW139 for PET imaging of neuroinflammation in vivo in the experimental autoimmune encephalomyelitis (EAE) model.

Altered secretory and neuroprotective function of the choroid plexus in progressive multiple sclerosis.

The choroid plexus (CP) is a key regulator of the central nervous system (CNS) homeostasis through its secretory, immunological and barrier properties. Accumulating evidence suggests that the CP plays a pivotal role in the pathogenesis of multiple sclerosis (MS), but the underlying mechanisms remain largely elusive. To get a comprehensive view on the role of the CP in MS, we studied transcriptomic alterations of the human CP in progressive MS and non-neurological disease controls using RNA sequencing.

Synthesis and Preclinical Evaluation of the First Carbon-11 Labeled PET Tracers Targeting Substance P.

Two potent SP peptidomimetics have been successfully radiolabeled via [C]CO-fixation with excellent yields, purity, and molar activity. l-[C]SP-peptidomimetic exhibited promising ex vivo biodistribution profile. Metabolite analysis showed that l-[C]SP-peptidomimetic is stable in brain and spinal cord, whereas rapid metabolic degradation occurs in rat plasma.

Prophylactic and therapeutic activity of alkaline phosphatase in arthritic rats: single-agent effects of alkaline phosphatase and synergistic effects in combination with methotrexate.

Alkaline phosphatase (AP) is a gate-keeper of innate immune system responses by detoxifying inflammation triggering moieties released from endogenous and external sources. We examined whether AP's broad mechanism of action constitutes a safe therapeutic, either as single agent or combined with methotrexate (MTX), for chronic inflammatory disorders, for example, rheumatoid arthritis (RA). A rat model for RA was used with repeated intra-articular methylated bovine serum albumin (mBSA) injections in 1 knee ("arthritic" knee), with the contralateral knee serving as internal control.

In-vivo monitoring of anti-folate therapy in arthritic rats using [F]fluoro-PEG-folate and positron emission tomography.

Background: Folate receptor β (FRβ) is involved in facilitating cellular uptake of folates and anti-folates (such as methotrexate (MTX)). In rheumatoid arthritis, FRβ is expressed on synovial macrophages and recently has been explored as a biomarker for imaging in arthritic rats using the folate-based positron emission tomography (PET) tracer [F]fluoro-PEG-folate. The purpose of this study was to examine whether this folate tracer can also be used to monitor therapeutic efficacy of MTX in arthritic rats.