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 ligand-SiFA conjugate compound represented by formula (1) wherein: R.sup.L is a ligand moiety which is capable of binding to prostate-specific membrane antigen (PSMA); R.sup.SiFA is a silicon-fluoride acceptor (SiFA) moiety which can be labeled with .sup.18F or which is labeled with .sup.18F; L is a linking moiety; R.sup.H is a hydrophilic moiety which comprises (i) a linear or branched sequence of 2 to 10 hydrophilic amino acid units A.sup.H, each of which is independently derived from a natural or non-natural amino acid carrying a hydrophilic side chain, and optionally one amino acid unit A.sup.N derived from a natural or non-natural amino acid which is devoid of a hydrophilic side chain, wherein the hydrophilic amino acid units and, if present, the unit A.sup.N, are bound to each other via a direct covalent bond or via a coupling unit; and which optionally further comprises (ii) one or more hydrophilic residues R.sup.T, each of which may be bound to an amino group, a carboxylic acid group, or to a hydrophilic side chain of an amino acid unit; or a pharmaceutically acceptable salt thereof.

##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.

The present invention relates to a pharmaceutical composition comprising a radiohybrid agent containing a silicon-fluoride and a chelating group wherein either the fluorine is .sup.18F or the chelating group contains a chelated radioactive metal, wherein the composition has a pH of 4.0-6.0 and further comprises: 0.1-200 mM citrate buffer; 1-100 mg/mL ethanol; and 5-10 mg/mL sodium chloride.

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.

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.

Presented herein are systems and methods that provide for improved computer aided display and analysis of nuclear medicine images. In particular, in certain embodiments, the systems and methods described herein provide improvements to several image processing steps used for automated analysis of bone scan images for assessing cancer status of a patient. For example, improved approaches for image segmentation, hotspot detection, automated classification of hotspots as representing metastases, and computation of risk indices such as bone scan index (BSI) values are provided.

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.

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.

Alkylphosphocholine analogs incorporating a chelating moiety that chelates a radioactive metal isotope are disclosed herein. The alkylphophocholine analogs, which can be used to treat or detect solid tumors, have the formula:

##STR00001##

R.sub.1 includes a chelating agent that is chelated to a metal atom, wherein the metal atom is a positron or single photon emitting metal isotope with a half life of greater than or equal to 4 hours, or an alpha, beta or Auger emitting metal isotope with a half life of greater than 6 hours and less than 30 days; a is 0 or 1; n is an integer from 12 to 30; m is 0 or 1; Y is H, OH, COOH, COOX, OCOX, or OX, wherein X is an alkyl or an arylalkyl; R.sub.2 is N.sup.+H.sub.3, N.sup.+H.sub.2Z, N.sup.+HZ.sub.2, or N.sup.+Z.sub.3, wherein each Z is independently an alkyl or an aroalkyl; and b is 1 or 2.