Methods for purifying .sup.89Zr are provided, .sup.89Zr compositions are provided, isotope compositions are provided that can include: a radio isotope and a nanoparticle, and methods for radio labeling monoclonal antibodies are provided.

A system, and method, for quantitatively mapping of mitochondrial membrane potential of a tissue in a subject is provided. In some aspects, the provided method includes administering to the subject a detectably effective amount of a tracer as an emission tomography imaging agent; acquiring, using an emission tomography system, emission tomography data associated with the tissue; analyzing the emission tomography data to determine a concentration distribution of the tracer within the tissue; correlating the concentration distribution of the tracer with the membrane potential of the tissue; determining, using the correlating step, a membrane potential distribution of the tissue; and generating a report indicating the membrane potential distribution of the tissue.

Described herein are nanoparticle conjugates that demonstrate enhanced penetration of tumor tissue (e.g., brain tumor tissue) and diffusion within the tumor interstitium, e.g., for treatment of cancer. Further described are methods of targeting tumor-associated macrophages, microglia, and/or other cells in a tumor microenvironment using such nanoparticle conjugates. Moreover, diagnostic, therapeutic, and theranostic (diagnostic and therapeutic) platforms featuring such nanoparticle conjugates are described for treating targets in both the tumor and surrounding microenvironment, thereby enhancing efficacy of cancer treatment. Use of the nanoparticle conjugates described herein with other conventional therapies, including chemotherapy, radiotherapy, immunotherapy, and the like, is also envisaged.

The present invention provides novel compounds that are useful as radiopharmaceuticals, imaging agents and for treatment of cancer.

This invention relates new radiopharmaceutical conjugates for use in improved methods of diagnosis and treatment of cancer. The radiopharmaceutical conjugate comprises, in sequence: a metabolite that targets tumour cells, bound to a chelating agent capable of containing a radionuclide, bound to a linker capable of binding with an EPR agent in vitro or in vivo; or a chelating agent capable of containing a radionuclide, bound to a metabolite that targets tumour cells, bound to a linker capable of binding with an EPR agent in vitro or in vivo. The radiopharmaceutical conjugates of the present invention provide active and passive targeted radio nuclide delivery systems that can help to improve the biodistribution and pharmacological toxicity of the radiopharmaceuticals used for the diagnosis and therapy of cancer.

This imaging method of AMPA receptors in the brain of primate organisms involves a step in which a substance which is administered to the primate organism and which selectively bonds to AMPA receptors in the brain of the primate organism and has a radiolabel is transported into the brain and made to bond with AMPA receptors in the brain, and, by detecting radiation emitted from the substance bonded to the AMPA receptors in the brain, data is obtained relating to the distribution and/or expression level of the AMPA receptors in the brain.

Radiolabeled anti-PD-L1 antibodies and their use in immuno-PET imaging are provided herein. Included are methods of detecting the presence of PD-L1 proteins in a patient or sample.

Dual-modality contrast agents are disclosed herein, having the general formula:

##STR00001##

R.sub.1 includes a chelating moiety that is chelated to a Mn.sup.2+ isotope. The disclosed contrast agents differentially target a wide range of malignant tumor tissues, and can be simultaneously used as contrast agents for both magnetic resonance imaging (MRI) and positron emission topography (PET) imaging. Accordingly, the disclosed contrast agent can be used in diagnosing and monitoring solid tumor cancers.

The present invention provides a method for the purification of .sup.227Th from a mixture comprising .sup.227Th and .sup.223Ra, said method comprising: i) preparing a first solution comprising a mixture of .sup.227Th and .sup.223Ra ions dissolved in an aqueous solution of first mineral acid; ii) loading said first solution onto a strong base anion exchange resin; iii) eluting .sup.223Ra from said strong base anion exchange resin using a second mineral acid in an aqueous solution; iv) optionally rinsing said strong base anion exchange resin using a first aqueous medium; v) eluting .sup.227Th from said strong base anion exchange resin using a third mineral acid in an aqueous solution whereby to generate a second solution comprising .sup.227Th. The invention further provides a purified .sup.227Th solution, a corresponding pharmaceutical formulation and methods of treatment of neoplastic disease.

Disclosed is a class of versatile Sarcophagine based bifunctional chelators (BFCs) containing a hexa-aza cage for labeling with metals having either imaging, therapeutic or contrast applications radiolabeling and one or more linkers (A) and (B). The compounds have the general formula ##STR00001## where A is a functional group selected from group consisting of an amine, a carboxylic acid, an ester, a carbonyl, a thiol, an azide and an alkene, and B is a functional group selected from the group consisting of hydrogen, an amine, a carboxylic acid, and ester, a carbonyl, a thiol, an azide and an alkene. Also disclosed are conjugate of the BFC and a targeting moiety, which may be a peptide or antibody. Also disclosed are metal complexes of the BFC/targeting moiety conjugates that are useful as radiopharmaceuticals, imaging agents or contrast agents.