PSMA targeted compounds, pharmaceutical compositions comprising these compounds, and methods for treating and detecting cancers in a subject are described herein.

The present invention relates to conjugates including a chelating moiety of a metal complex thereof and a therapeutic or targeting moiety, methods for their production, and uses thereof.

The present invention relates to formulations of radiolabelled compounds that are of use in radiotherapy and diagnostic imaging.

The one subject of the invention is the compounds of general formula (I), their isomers, their physiologically acceptable salts and/or Mn(II), Fe(II), Fe(III), Co(II) and Ni(II) complexes. The other subject of the invention is the application of the above compounds. The compounds of general formula (I): wherein R.sub.a refers to OH group or NR.sub.3R.sub.4 group and NR.sub.3R.sub.4 group may refer to: a) NR.sub.3R.sub.4 with N atom in the ring means a ring of 4 to 7, that in certain cases may contain another heteroatom, and in specific cases the ring may be replaced with an aryl group (of 5 to 7 carbon atoms) substituted with COOH, OH, OCH.sub.3, NO.sub.2, NH.sub.2, NCS, NHS activated ester, aryl (of 5 to 7 carbon atoms), or nitro-, amino- or isothiocyanate group, or b) in the NR.sub.3R.sub.4 group R.sub.3 means a H atom, alkyl, aryl, nitroaryl, aminoaryl or isothiocyanate-aryl group (of 1 to 6 carbon atoms) and R4 is a H atom, alkyl (of 1 to 6 carbon atoms) or (CH.sub.2).sub.nCOOH group, whereas n=1 to 10 integer, or c) NR.sub.3R.sub.4 group is one of the below groups: whereas R.sub.1 is a H atom, carboxyl or alkyl-carbonyl group (of 1 to 4 carbon atoms); and R.sub.b is a H atom or alkyl group (of 1 to 6 carbon atoms), and X means independently from one another H atom, CH.sub.3, COOH, OH, OCH.sub.3, alkoxy- (of 2 to 6 carbon atoms), NO2, NH2, NCS, NHS-activated ester, alkyl (of 2 to 12 carbon atoms) or aryl (of 5 to 7 carbon atoms) group, in certain cases the latter may be substituted with hydroxyl, hydroxyalkyl (of 1 to 6 carbon atoms), nitro, amino or isothiocyanate group; and Y means: NH or >NCH.sub.2Z group, whereas in the >CH.sub.2Z group Z refers to one selected group of the below: C(O)NR.sub.3R.sub.4 group, in which NR.sub.3R4 means as referred to above, whereas z=0-18 integer, whereas z=0-18 integer, whereas z=0-18 integer, whereas z=0-18 integer and H atom, alkyl (of 1 to 6 carbon atoms) or (CH.sub.2).sub.nCOOH group, whereas n=1 to 10 integer, or, whereas z=0-18 integer, whereas z=0-18 integer and R.sub.2a refers to H atom, OCH.sub.3, or CF.sub.3 group, whereas R.sub.2b refers to H atom, CH.sub.3, OCH.sub.3>.CF.sub.3; COOH, COON(CO).sub.2(CH.sub.2).sub.2, NO.sub.2, NH.sub.2 or NCS group, whereas z=0-18 integer and R.sub.2c refers to H atom, NO.sub.2, NH.sub.2 or NCS group, whereas =0-18, -and x=1-5 integer, whereas z=0-18. and x=1.5 integer; whereas z=1-5, and x=1-5 integer, R.sub.2d refers to H atom, CH.sub.3, OCH.sub.3;.CF.sub.3, COOH, COON(CO).sub.2(CH.sub.2).sub.2, NO.sub.2, NH.sub.2 or NCS group,

##STR00001## ##STR00002##

Imaging and radiotherapeutics agents targeting fibroblast-activation protein-? (FAP-?) and their use in imaging and treating FAP-? related diseases and disorders are disclosed.

Imaging and radiotherapeutics agents targeting fibroblast-activation protein-? (FAP-?) and their use in imaging and treating FAP-? related diseases and disorders are disclosed.

Compounds derived from celecoxib, valdecoxib, and indomethacin, and methods of use thereof, are disclosed. The compounds are useful for, inter alia, identifying and localizing the site of pathology and/or inflammation responsible for the sensation of pain in a patient; for identifying the sites of primary, secondary, benign, or malignant tumors; and for diagnosing infection or confirming or ruling out suspected infection. The compounds contain a radioactive agent which permits imaging. The compounds concentrate at sites of increased cyclooxygenase expression, such as areas of increased COX-2 expression, thus revealing the sites of increased prostaglandin production, which is correlated with pain and inflammation, and correlated with tumor presence and/or location. Identifying areas of increased COX expressing can also aid in screening for infections, assessing efficacy of diagnosis and treatment of rheumatoid arthritis, and assessing the need for treatment with opioid drugs.

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.

The present invention describes new compounds that are useful for image-guided surgery and photodynamic therapy. In particular the compounds may be targeted to the nucleus or the mitochondria after compounds were delivered to diseased tissues such as cancer using a ligand that target receptor that express on the diseased tissue and followed by receptor mediated endocytosis and provide effective activity against cancer cells as well as other disorders. Methods and compositions for use of the same are described.

Compounds comprising a tetrapyrrole macrocycle that includes a radionuclide; a hydrogelator attached to the tetrapyrrole macrocycle; a water solubilizing group attached to the hydrogelator; and a cleavage site that is between the hydrogelator and the water solubilizing group are described herein along with their methods of use. Two or more compounds of the present invention may two or more compounds may self-assemble (e.g., aggregate), optionally in vivo.