New methodologies for site-specifically radiolabeling proteins with the PET isotope [.sup.1SF] are required to generate high quality radiotracers for imaging in both the preclinical and clinical settings. The enzymatic radiofluorination overcomes many of the limitations encountered to date with purely chemical approaches. The bacterial enzyme lipoic acid ligase was used to conjugate [.sup.18F]-fluorooctanoic acid to both a small peptide and a Fab antibody fragment. Labeling was site-specific and highly efficient under mild aqueous conditions using small amounts of peptide/protein (1-10 nmol). The labeled construct retained full epitope binding affinity and was stable in mouse serum. Using an optimized reaction scheme, mCi quantities of [.sup.18F]-Fab were generated, an amount sufficient for human imaging.

New methodologies for site-specifically radiolabeling proteins with the PET isotope [.sup.1SF] are required to generate high quality radiotracers for imaging in both the preclinical and clinical settings. The enzymatic radiofluorination overcomes many of the limitations encountered to date with purely chemical approaches. The bacterial enzyme lipoic acid ligase was used to conjugate [.sup.18F]-fluorooctanoic acid to both a small peptide and a Fab antibody fragment. Labeling was site-specific and highly efficient under mild aqueous conditions using small amounts of peptide/protein (1-10 nmol). The labeled construct retained full epitope binding affinity and was stable in mouse serum. Using an optimized reaction scheme, mCi quantities of [.sup.18F]-Fab were generated, an amount sufficient for human imaging.

Provided herein are hypoxia inducible factor 2-alpha (HIF-2α)-specific radioactive tracers, methods of use thereof, and methods of synthesis thereof. Specifically, provided herein are HIF-2α-specific radioactive tracers comprising an HIF-2α-specific agent developed as a therapeutic inhibitor and a positron emitting radioactive label. Embodiments provide methods of detecting an HIF-2α-expressing tumor, detecting an HIF-2α inhibitor resistant tumor, evaluating a change in HIF-2α expression in response to an anti-cancer treatment, detecting acquisition of HIF-2α inhibitor resistance, evaluating efficacy of an HIF-2α depletion therapy, or detecting or monitoring an ischemic area in a subject. Also provided are methods of synthesizing an HIF-2α-specific radioactive tracer.

Provided herein are hypoxia inducible factor 2-alpha (HIF-2α)-specific radioactive tracers, methods of use thereof, and methods of synthesis thereof. Specifically, provided herein are HIF-2α-specific radioactive tracers comprising an HIF-2α-specific agent developed as a therapeutic inhibitor and a positron emitting radioactive label. Embodiments provide methods of detecting an HIF-2α-expressing tumor, detecting an HIF-2α inhibitor resistant tumor, evaluating a change in HIF-2α expression in response to an anti-cancer treatment, detecting acquisition of HIF-2α inhibitor resistance, evaluating efficacy of an HIF-2α depletion therapy, or detecting or monitoring an ischemic area in a subject. Also provided are methods of synthesizing an HIF-2α-specific radioactive tracer.

Provided herein are bifunctional compounds that bind tau protein and/or promote targeted ubiquitination for the degradation of tau protein. In particular, provided are compounds that can bind tau protein, a protein whose aggregation is implicated in a variety of neurodegenerative disease (e.g., tauopathies), and can promote its degradation by recruiting an E3 ubiquitin ligase (e.g., Cereblon), which can ubiquitinate tau protein, marking it for proteasomal degradation. Also provided are radiolabeled forms of the bifunctional compounds, pharmaceutical compositions comprising the bifunctional compounds, methods of detecting and/or diagnosing neurological disorders, methods of detecting and/or diagnosing pathological aggregation of tau protein (e.g., in the central nervous system), methods of treating and/or preventing neurological disorders, and methods of promoting the degradation of tau protein by E3 ubiquitin ligase activity in a subject by administering a compound or composition described herein.

Provided herein are bifunctional compounds that bind tau protein and/or promote targeted ubiquitination for the degradation of tau protein. In particular, provided are compounds that can bind tau protein, a protein whose aggregation is implicated in a variety of neurodegenerative disease (e.g., tauopathies), and can promote its degradation by recruiting an E3 ubiquitin ligase (e.g., Cereblon), which can ubiquitinate tau protein, marking it for proteasomal degradation. Also provided are radiolabeled forms of the bifunctional compounds, pharmaceutical compositions comprising the bifunctional compounds, methods of detecting and/or diagnosing neurological disorders, methods of detecting and/or diagnosing pathological aggregation of tau protein (e.g., in the central nervous system), methods of treating and/or preventing neurological disorders, and methods of promoting the degradation of tau protein by E3 ubiquitin ligase activity in a subject by administering a compound or composition described herein.

The invention provides high-sensitivity methods for detection and quantification of target analytes in liquid samples (e.g., biological or environmental samples). The methods can be multiplexed to allow simultaneous detection and quantification of multiple target analytes that are contained in the same sample. The invention also provides related compositions and kits.

The invention is directed to a synthetic particle antibody comprising a bi-functional particle framework, such as for example and not limitation, a Janus micro- or nanoparticle, wherein one side of the bi-functional particle comprises targeting ligands (such as for example and not limitation, a protein, a peptide, an aptamer, and/or fragments thereof, wherein the at least one targeting ligand has the ability to specifically bind to a desired cell or tissue type in a subject's body) and the other side of the bi-functional particle comprises immune-activating ligands (such as for example and not limitation, fragments of the Fc portion of antibodies, immune-activating peptides, immune-activating aptamers, and other proteins, peptides or nucleic acids that mimic the structure and/or function of the Fc portion of antibodies).

The invention is directed to a synthetic particle antibody comprising a bi-functional particle framework, such as for example and not limitation, a Janus micro- or nanoparticle, wherein one side of the bi-functional particle comprises targeting ligands (such as for example and not limitation, a protein, a peptide, an aptamer, and/or fragments thereof, wherein the at least one targeting ligand has the ability to specifically bind to a desired cell or tissue type in a subject's body) and the other side of the bi-functional particle comprises immune-activating ligands (such as for example and not limitation, fragments of the Fc portion of antibodies, immune-activating peptides, immune-activating aptamers, and other proteins, peptides or nucleic acids that mimic the structure and/or function of the Fc portion of antibodies).

The present disclosure provides methods for proximity-induced antibody conjugation of target agents).