The radiopharmaceutical .sup.177Lu-PSMA I&T is provided, including in high purities with extended shelf life. Further provided are methods of synthesis of .sup.177Lu-PSMA I&T and pharmaceutical compositions and methods of treatment that comprise .sup.177Lu-PSMA I&T.

The present invention provides a composition comprising anti-1-amino-3-.sup.18F-fluorocyclobutyl-1-carboxylic acid (.sup.18F-FACBC) having an improved impurity profile compared with previous such compositions. Also provided is a method to obtain said composition.

Disclosed are compositions and methods relating to prostate cancer. In particular, disclosed are bivalent targeting ligands that specifically bind prostate specific membrane antigen and gastrin-releasing peptide receptor. Bivalent binding agents disclosed herein can be used to image a tissue in a subject in need thereof and to diagnose prostate cancer in a subject in need thereof. Bivalent binding agents disclosed herein can be used to treat prostate cancer in a subject in need thereof.

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 combinations for use and methods of treating cancers that express prostate specific membrane antigen (PSMA). In particular, the invention provides novel therapies based on the combination of a PSMA therapeutic agent, such as radiolabeled Compound of the Formula I, and immuno-oncology (I-O) therapeutic agents, wherein said I-O therapeutic agents are selected from the group consisting of LAG-3 inhibitors, TIM-3 inhibitors, GITR agonists, TGF-β inhibitors, IL15/IL-15RA complex, PD-1 inhibitors, PD-L1 inhibitors, and CTLA-4 inhibitors.

[Problem]

Provided is a labeled fatty acid derivative for diagnostic imaging that enables quantification of fatty acid metabolic activity in the heart muscle.

[Means for Solution]

The present inventors have conducted intensive investigations on a method that enables quantification of fatty acid metabolic activity and thus have found that a labeled fatty acid derivative typified by 3-{[(5Z)-3-[.sup.18F]fluorotetradeca-5-en-1-yl]sulfanyl}propanoic acid or a salt thereof has excellent accumulation to the heart muscle and thus enables imaging of fatty acid metabolic activity by positron emission tomography (PET). Therefore, the labeled fatty acid derivative of the present invention can be used as a radiolabeled tracer for rapid and non-invasive quantification of fatty acid metabolic activity in the heart muscle, diagnostic imaging of heart disease typified by an ischemic heart disease, diagnostic imaging of the therapeutic effect of a therapeutic drug for heart disease, and the like.

Methods for co-injection of a non-radioactive PSMA inhibitor, referred to herein as a competing inhibitor (CI), with a radiolabeled PSMA inhibitor are disclosed. This combination reduces the uptake of the radiotracer in non-target organs, including the kidneys and lacrimal glands, with only a modest reduction in tumor uptake.

A compound comprising a prostate specific membrane antigen (PSMA)-targeting moiety of the following formula or of a salt or a solvate thereof. R.sup.0 is O or S. Each of R.sup.1a, R.sup.1b and R.sup.1c may be —CO.sub.2H, —SO.sub.2H, —SO.sub.3H, —PO.sub.2H, or —PO.sub.3H.sub.2, for example. R.sup.2 may be methylene or a derivative thereof, propylene or a derivative thereof, or a derivative of ethylene, optionally substituted. R.sup.3 is a linker. When the PSMA-targeting moiety is linked to a radiolabeling group, the compound may be used as an imaging agent or therapeutic agent for PSMA-expressing diseases/conditions.

##STR00001##

The present technology provides compounds, as well as compositions including such compounds, useful for imaging and/or treatment of a glioma, a breast cancer, an adrenal cortical cancer, a cervical carcinoma, a vulvar carcinoma, an endometrial carcinoma, a primary ovarian carcinoma, a metastatic ovarian carcinoma, a non-small cell lung cancer, a small cell lung cancer, a bladder cancer, a colon cancer, a primary, gastric adenocarcinoma, a primary colorectal adenocarcinoma, a renal cell carcinoma, and/or a prostate cancer.

The present disclosure relates to methods for radiolabelling PSMA binding ligands with a radioactive isotope, preferably .sup.68Ga, .sup.67Ga or .sup.64Cu, and their kits.