Preclinical Positron Emission Tomography (PET) of Prosthetic Joint Infection Using a Nitro-Prodrug of 2-[F]F--Aminobenzoic Acid ([F]F-PABA).

Deep-seated bacterial infections are difficult to detect and diagnose due to the lack of specific clinical imaging modalities. Therefore, the bacteria-specific positron emission tomography radiotracer 2-[F]fluoro-4-nitrobenzoic acid ([F]FNB) was developed, which is reduced to 2-[F]fluoro-4-aminobenzoic acid ([F]F-PABA) by bacterial nitroreductases and has improved pharmacokinetics compared to the parent compound. PET imaging demonstrated that the uptake of 2-[F]fluoro-4-nitrobenzoic acid in a clinically relevant prosthetic joint infection model was up to ∼4-fold higher in the infected joint compared to the contralateral joint.

Pretargeting with Cucurbituril-Adamantane Host-Guest Pair in Xenograft Models.

The goal of reducing the total-body radiation dose of macromolecule-based nuclear medicine with a 2-step pretargeting strategy has been achieved with several pretargeting methodologies in preclinical and clinical settings. However, the lack of modularity, biocompatibility, and in vivo stability in existing pretargeting agents obstructs their respective platforms' wide clinical use. We hypothesized that host-guest chemistry would provide an optimal pretargeting methodology.

PET Imaging of Leg Arteries for Determining the Input Function in PET/MRI Brain Studies Using a Compact, MRI-compatible PET System.

In this study, we used a compact, high-resolution, and MRI-compatible PET camera (VersaPET) to assess the feasibility of measuring the image-derived input function (IDIF) from arteries in the leg with the ultimate goal of enabling fully quantitative PET brain imaging without blood sampling. We used this approach in five F-FDG PET/MRI brain studies in which the input function was also acquired using the gold standard of serial arterial blood sampling. After accounting for partial volume, dispersion, and calibration effects, we compared the metabolic rates of glucose (MRglu) quantified from VersaPET IDIFs in 80 brain regions to those using the gold standard and achieved a bias and variability of <5% which is within the range of reported test-retest values for this type of study.

Evaluation of a Radio-IMmunoStimulant (RIMS) in a Syngeneic Model of Murine Prostate Cancer and ImmunoPET Analysis of T-cell Distribution.

An immunosuppressive tumor microenvironment and tumor heterogeneity have led to the resilience of metastatic castrate resistant prostate cancer (mCRPC) to current treatments. To address these challenges, we developed and evaluated a new drug paradigm, Radio-IMmunostimulant (RIMS), in a syngeneic model of murine prostate cancer. RIMS-1 was generated using a convergent synthesis employing solid phase peptide and solution chemistries.

Investigation of Copper-64-Based Host-Guest Chemistry Pretargeted Positron Emission Tomography.

Pretargeting is a technique that uses macromolecules as targeting agents for nuclear imaging and therapy with the goal of reducing the radiation toxicity to healthy tissues often associated with directly radiolabeled macromolecules. In pretargeting, a macromolecule is radiolabeled at the target site using a radiolabeled small molecule (radioligand) that interacts with the macromolecule with high specificity. We report an investigation of host-guest chemistry-driven pretargeting using copper-64 radiolabeled ferrocene (Fc; guest) compounds and a cucurbit[7]uril (CB7; host) molecule functionalized carcinoembryonic antigen targeting hT84.