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 disclosed method of treating a malignant solid tumor in a subject includes the steps of administering to the subject an immunomodulatory dose of a radioactive phospholipid ether metal chelate, a radiohalogenated phospholipid ether, or other targeted radiotherapy (TRT) agent that is differentially retained within malignant solid tumor tissue, and either (a) performing in situ tumor vaccination in the subject by introducing into at least one of the malignant solid tumors one or more agents capable of stimulating specific immune cells within the tumor microenvironment, or (b) performing immunotherapy in the subject by systemically administering to the subject an immunostimulatory agent, such as an immune checkpoint inhibitor. In a non-limiting example, the radioactive phospholipid ether metal chelate or radiohalogenated phospholipid ether has the formula:

##STR00001##

wherein R.sub.1 comprises a chelating agent that is chelated to a metal atom, wherein the metal atom is an alpha, beta or Auger emitting metal isotope with a half-life of greater than 6 hours and less than 30 days, or wherein R.sub.1 comprises a radioactive halogen isotope. In one such embodiment, a is 1, n is 18, m is 0, b is 1, and R.sub.2 is —N.sup.+(CH.sub.3).sub.3.

Disclosed herein is a fractionated dosing regimen of .sup.131I-labeled 18-(p-iodo-phenyl)octadecyl phosphocholine for the treatment of cancer.

The invention relates to therapeutic nanobiologic compositions and methods of treating patients who have had an organ transplant, or who suffer from atherosclerosis, arthritis, inflammatory bowel disease including Crohn's, autoimmune diseases including diabetes, and/or autoinflammatory conditions, or after a cardiovascular events, including stroke and myocardial infarction, by inhibiting trained immunity, which is the long-term increased responsiveness, the result of metabolic and epigenetic re-wiring of myeloid cells and their stem cells and progenitors in the bone marrow and spleen and blood induced by a primary insult, and characterized by increased cytokine excretion after re-stimulation with one or multiple secondary stimuli.

The invention relates to therapeutic nanobiologic compositions and methods of treating patients who have had an organ transplant, or who suffer from atherosclerosis, arthritis, inflammatory bowel disease including Crohn's, autoimmune diseases including diabetes, and/or autoinflammatory conditions, or after a cardiovascular events, including stroke and myocardial infarction, by inhibiting trained immunity, which is the long-term increased responsiveness, the result of metabolic and epigenetic re-wiring of myeloid cells and their stem cells and progenitors in the bone marrow and spleen and blood induced by a primary insult, and characterized by increased cytokine excretion after re-stimulation with one or multiple secondary stimuli.

Disclosed herein are methods of treating a tumor or cancer in a subject whose tumor or cancer cells express low levels of asparagine synthetase (ASNS), and compounds and compositions useful in such treatment. Also disclosed herein are methods of evaluating whether to administer a compound that inhibits glutathione production or a glutaminase inhibitor to a subject with a tumor or cancer.

A method of treating a malignant solid tumor in a subject is disclosed herein. The method includes the steps of administering to the subject an immunomodulatory dose of a radiohalogenated compound that is differentially taken up by and retained within malignant solid tumor tissue, and performing in situ tumor vaccination in the subject by intratumorally injecting into (or treating via a separate method) at least one of the malignant solid tumors a composition that includes one or more agents capable of stimulating specific immune cells within the tumor microenvironment. In certain exemplary embodiments, the radiohalogenated compound has the formula:

##STR00001##

wherein R.sub.1 is a radioactive halogen isotope, n is 18 and R.sub.2 is N.sup.+(CH.sub.3).sub.3.

The disclosed method of treating a malignant solid tumor in a subject includes the steps of administering to the subject an immunomodulatory dose of a radioactive phospholipid metal chelate compound that is differentially retained within malignant solid tumor tissue, and performing in situ tumor vaccination in the subject by introducing into at least one of the malignant solid tumors one or more agents capable of stimulating specific immune cells within the tumor microenvironment, or by performing another method of in situ tumor vaccination. In a non-limiting example, the radioactive phospholipid metal chelate compound has the formula:

##STR00001##

wherein R.sub.1 comprises a chelating agent that is chelated to a metal atom, wherein the metal atom is an alpha, beta or Auger emitting metal isotope with a half life of greater than 6 hours and less than 30 days. In one such embodiment, a is 1, n is 18, m is 0, b is 1, and R.sub.2 is N.sup.+(CH.sub.3).sub.3.

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.

Presented herein are methods and compositions for non-invasive imaging of TAMs with discoidal high-density lipoproteins to assess prognosis and therapy outcome. TAMs are increasingly investigated in cancer immunology, and are considered a promising target for better and tailored treatment of malignant growths. Although TAMs also have high diagnostic and prognostic value, TAM imaging still remains largely unexplored. Imaging agents/methods provided herein are of value for non-invasive in vivo evaluation of TAM burden, not only in preclinical but also in clinical settings.