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.

A precursor compound of a radiolabeled compound as shown in Formula (I), a radiolabeled compound thereof, or a pharmaceutically acceptable salt thereof. The radiolabeled compound is high in water solubility, good in in-vitro stability at room temperature, and high in plasma protein binding rate, and shows high and long-time bone uptake in both in-vivo distribution in mice and imaging of New Zealand rabbits, and animal experiments show that the development effect is better than that of .sup.99mTc-MDP.

The invention provides compounds that inhibit cholinesterases, such as acetylcholinesterase and butyrylcholinesterase. Such compounds are useful to prevent or treat exposure of a patient (e.g., a human) to an organophosphoric nerve agent (e.g., sarin and VX) or to treat a patient suffering from a neurodegenerative disorder such as Alzheimer's Disease or Lewy Body Dementia. The compounds are further useful as diagnostic tools for use in medical or research radiography (e.g., positron emission tomography) when synthesized with a radionuclide (e.g., [18F]. Synthetic schemes to produce such compounds are also provided.

Compounds as defined herein are provided which are useful in (1) diagnostic methods for detecting and/or identifying cells presenting PSMA; (2) compositions comprising a compound of the invention together with a pharmaceutically acceptable diluent; and (3) methods for imaging prostate cancer cells.

##STR00001##

Described herein are prostate specific membrane antigen (PSMA) binding conjugates that are useful for delivering therapeutic, diagnostic and imaging agents. Also described herein are pharmaceutical composition containing them and methods of using the conjugates and compositions. Also described are processes for manufacture of the conjugates and the compositions containing them.

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 present invention relates to compounds according to Formula I or Formula II, which are potential bone imaging agents. Certain compounds labeled with .sup.68Ga displayed excellent bone uptake and retention. The present invention also relates to pharmaceutical compositions comprising a pharmaceutical acceptable carrier and a compound of Formula I or Formula II or a pharmaceutically acceptable salt thereof.

##STR00001##

The present invention provides methods and uses of phospholipid ether analogs as diagnostic and therapeutic agents for numerous 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 R1 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 R1 comprises a radioactive halogen isotope. In one such embodiment, a is 1, n is 18, m is 0, b is 1, and R2 is N+(CH3)3.

A diphosphine precursor compounds of Formula (I), conjugates thereof of Formula (H) and radionuclide conjugate complexes thereof are disclosed herein. The compounds are advantageous at least because they enable the easy one-step extemporaneous preparation of the corresponding complexes in the clinic in high radiochemical yields and under mild conditions. Also disclosed are the methods of making the compounds and complexes herein along with their uses. The complexes are particularly useful in the field of medicine and diagnosis, such as in medical imaging and targeted payload delivery.

##STR00001##