The present invention relates to compounds that are useful as metal ligands and which either contain a molecular recognition moiety or can be bound to a molecular recognition moiety and methods of making these compounds. Once the compounds that contain a molecular recognition moiety are coordinated with a suitable metallic radionuclide, the coordinated compounds are useful as radiopharmaceuticals in the areas of radiotherapy and diagnostic imaging. The invention therefore also relates to methods of diagnosis and therapy utilising the radiolabelled compounds of the invention.

An environmentally sensitive membrane binding polypeptide, pH (low)-sensitive membrane peptide (pHLIP) has improved insertion kinetics balanced with solubility to selectively target acidic tissues.

The present disclosure relates to a liquid pharmaceutical formulation comprising a DOSA-derived tetra-chelate of formula (I), in which M is an ion of a paramagnetic metal, preferably a Gd.sup.3+ ion, and R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as defined in the claims, in a pharmaceutical acceptable solvent. The present disclosure also relates to a method of preparation of said liquid pharmaceutical formulation and to a method of imaging involving said liquid pharmaceutical formulation.

An imaging nanoparticle comprising a plant virus particle having an interior surface and an exterior surface, an imaging agent that is linked to the interior and/or exterior surface, and a layer of biocompatible mineral such as silica coated over the exterior surface, is described. The imaging nanoparticle can be used in method of generating an image of a tissue region of a subject, by administering to the subject a diagnostically effective amount of an imaging nanoparticle and generating an image of the tissue region of the subject to which the imaging nanoparticle has been distributed.

The invention provides a (drug-containing) lipid nanoparticle with: (i) at least one phospholipid; (ii) at least one lysolipid; and (iii) at least one phospholipid comprising a hydrophilic polymer; and (iv) at least one structural lipid of formula (I) which has the following general structure: ##STR00001## wherein R and R′ are long hydrocarbyl hydrophobic chains, Y is a linker element, and PHG is a polar head group described as large according to its van der Waals radius, and which is different from the phospholipid (i). The lipid nanoparticle can release a drug (or API) from within the lipid nanoparticle as a result of focused ultrasound (FUS) applied continuously, at least twice, to a desired part of the body to induce hyperthermia (an increase in temperature). FUS is applied after the lipid nanoparticle containing the drug has been administered to the live subject, and causes controlled release of the drug at the desired site of the body. Ultrasound is then halted, and the site of interest allowed to cool. Ultrasound is then applied again. Lipid nanoparticles can be labelled (for MRI, NIRF imaging), enabling real time monitoring of the drug in the human body. Imaging information can be used to direct and guide the nature of the FUS applied to the site of interest.

A liposomal composition (“ADx-003”) is provided, ADx-003 comprising a first phospholipid; a sterically bulky excipient that is capable of stabilizing the liposomal composition; a second phospholipid that is derivatized with a first polymer; a macrocyclic gadolinium-based imaging agent; and a third phospholipid that is derivatized with a second polymer, the second polymer being conjugated to a targeting ligand, the targeting ligand being represented by Formula I: ##STR00001##
wherein X is —CH.sub.2—, —CH.sub.2—CH.sub.2—, —CHO—, or —O—CO—; Y is —CH—CH═CH— or ##STR00002##
A and B are independently selected from C and N; R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are independently selected from —H, halogen, —OH, and —CH.sub.3; and R.sub.5, R.sub.6, and R.sub.7 are independently selected from —H, halogen, —OH, —OCH.sub.3, —NO.sub.2, —N(CH.sub.3).sub.2, C.sub.1-C.sub.6 alkyl, or a substituted or unsubstituted C.sub.4-C.sub.6 aryl group, except that when A and/or B is N the adjacent R.sub.5 and/or R.sub.7 is —H, or a pharmaceutically acceptable salt thereof.

Alkylphosphocholine analogs incorporating a chelating moiety that is chelated to gadolinium are disclosed herein. The alkylphophocholine analogs are compounds having the formula:

##STR00001##

or a salt therof. R.sub.1 includes a chelating agent that is chelated to a gadolinium atom; 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. The compounds can be used to detect solid tumors or to treat solid tumors. In detection/imaging applications, the gadolinium emits signals that are detectable using magnetic resonance imaging. In therapeutic treatment, the gadolinium emits tumor-targeting charged particles when exposed to epithermal neutrons.

Methods of preparing .sup.18F targeting biomolecules and small molecules with biological activity for therapeutic and/or diagnostic applications using fluorinated aromatic compounds. A fluorinated conjugated target tracer is synthesized and purified with temperature and solvent conditions that are mild for the tracer molecule. The purified fluorinated-conjugated target tracer is then labeled with .sup.18F using .sup.18F salts within a short reaction time, and with temperature and solvent conditions that are mild for the tracer molecule. The method provides a quick and convenient process that maintains the biological activities of the target molecules. The radio-labeled biomolecules may be used as contrast agents for Positron Emission Tomography (PET).

The present application provides a compound comprising at least one isotopically labeled nitrogen atom for use in diagnosing a condition or disease in a subject, compositions and kits comprising the compound and methods of using the same.

Polarized nuclear imaging and spectroscopy systems and methods are disclosed. In some embodiments, nuclei of a radioactive substance are polarized such that the spins of the nuclei are oriented in a specific direction, to generate a polarized radioactive tracer with anisotropic gamma ray emission. The radioactive substance is selected such that the degree of anisotropy is enhanced. A tracer is introduced into a living subject for delivery to a target area of interest in the subject. The tracer is delivered such that nuclear spin relaxation of the tracer is inhibited during transport of the tracer to the target area of interest. Gamma rays from the gamma ray emission are detected, and based on the detected gamma rays and properties associated with the anisotropic gamma ray emission, imaging data and/or spectroscopic data are obtained that are associated with the tracer in the subject. In some embodiments, a radioactive substance is delivered to a target area of interest in the subject and the nuclei of the radioactive substance are polarized following delivery of the radioactive substance to the target area of interest, such that the spins of the nuclei are oriented in a specific direction, to generate a polarized radioactive tracer with anisotropic gamma ray emission. Gamma rays are detected from the gamma ray emission, and based on the detected gamma rays and properties associated with the anisotropic gamma ray emission, imaging data and/or spectroscopic data are obtained that are associated with the tracer in the subject.