Abstract: Novel 18F-labelled tetrazines are provided which are highly reactive to be effective in vivo, suitable for pretargeted positron emission tomography (PET) and accessible in radiochemical yields (RCYs) which allow access to 18F-labeled tetrazines for clinical applications. The 18F-labelled tetrazines are developed using a Cu-mediated click indirect labelling approach. Only a subset of compounds appeared to be suitable for clinical pretargeted imaging strategies, and a particular compound which includes the use of an 18F-labelled azide synthon having an azide structure with glucose as the linker and a triazole moiety within the linker, appears to be highly suited for clinical pretargeted imaging purposes.

Abstract: The present invention relates to positron-emitting imaging agents for use in the prognosis of a neuroendocrine neoplasm (NEN) patient in by PET imaging of the cancer, wherein said imaging agent comprises a uPAR binding peptide coupled via the chelating agent NOTA or DOTA to the radionuclide 68Ga or 64Cu. The invention also relates to compositions comprising a radiopharmaceutical for use in the treatment or alleviation of a neuroendocrine neoplasm (NEN) in a subject, wherein said radiopharmaceutical comprises a radionuclide and a uPAR binding peptide.

Abstract: The invention regards a method for 18F-labeling of a peptide.

Abstract: The present invention relates to novel tetrazine compounds for use in pretargeted in vivo imaging and in therapy and to the precursors of the tetrazine compounds. The compounds are suitable for use in click chemistry. i.e. reactions that join a targeting molecule and a reporter molecule. The compounds comprise a radionuclide of F, I or At and on or more polar groups providing that the compounds can efficiently react with extracellularly located pretargeting vectors and as such used for example for pretargeted cancer diagnostics and cancer therapy.

Abstract: Up until now, only low reactivity Tzs can be radiolabeled via direct aliphatic SN2. Unfortunately, these structures display too low reactivity for in vivo bioorthogonal chemistry approaches. Highly reactive structures such as mono-unsubstituted tetrazines (H-Tzs) have been reported to be highly sensitive to base. Extensive degradation is observed which prevents isolation of meaningful amounts for imaging studies. In the present invention there is provided a method providing the possibility to radiolabel base sensitive tetrazine structures with significantly improved RCYs. Even tetrazines that were previously not accessible by applying “standard” aliphatic 18F-labeling strategies can be radiolabeled. This places new classes of 18 F-fluorinated compounds within reach for application in PET imaging studies such as for diagnosis of cancers.

Abstract: The present invention describes Urokinase Plasminogen Activator Receptor (uPAR) targeted radiolabeled conjugates suited for non-invasive PET imaging, SPECT imaging or targeted radionuclide therapy. In particular, but not limited to, the invention related to imaging and therapy of cancer diseases.

Abstract: Provided herein are methods for reducing fructose uptake in a subject; as well as associated compositions. The compositions are useful in therapeutic and non-therapeutic uses such as appetite suppression and treating or preventing metabolic syndrome, obesity, non-alcoholic fatty liver disease, and constipation.

Abstract: The present invention provides extracorporeal removal of targeting vectors applied in pretargeted therapy and diagnostics in animals and humans. The method and the means for extracorporeal removal of the targeting vectors is based on binding agents with inverse electron demand Diels-Alder (IEDDA) cycloaddition reactivity. The targeting vector comprises a therapeutic agent, a diagnostic agent or a theranostic agent and a chemical entity with IEDDA reactivity whereas the extracorporeal means comprises a column with a biocompatible solid support to which a chemical entity with complementary IEDDA reactivity is attached.

Abstract: The present invention provides novel PSMA targeting urea-based ligands that binds to prostate-specific membrane antigen (PSMA) which is expressed 8-to-12-fold higher in prostate cancer cells when compared to healthy tissue. The PSMA targeting urea-based ligands comprises a chelating agent that may comprise a metal and a halogen radioisotope of fluorine, iodine, bromine or astatine. The invention further relates to a method for providing the PSMA targeting urea-based ligands of the invention, to precursors of the PSMA targeting urea-based ligands and to the PSMA targeting urea-based ligands use in radiotherapy, imaging and theranostic.

Abstract: There is provided a 177-Lu labelled peptide for site-specific targeting of TF thereby enabling treatment of a cancer disease associated with high TF expression; e.g. treatment of cancer by administering to a patient an effective amount of the 177-Lu labelled peptide.

Abstract: The present invention describes a composition comprising a fluorophore labelled uPAR-targeting component, a buffer and a surfactant, wherein the fluorophore labelled uPAR-targeting component is solubilized in the composition by means of the surfactant being present, and wherein the composition comprises a maximum of 10 wt % water, preferably a maximum of 5 wt % water.

Abstract: The present invention relates to tumor-targeted probes for use as medicaments and for use in treatment of cancer and to methods of treatment wherein such probes are used. The probes consist of a light-absorbing molecule linked directly or via a spacer to a peptide targeting the urokinase-type plasminogen activator receptor (uPAR). When irradiating the light-absorbing molecule of the probe with laser beams from an external source heat will be released locally to tumor cells expressing uPAR resulting in tumor ablation.

Abstract: The present invention describes a uPAR-targeting peptide conjugate comprising a fluoro bore, a peptide binding to uPAR and a linker group which are connected by covalent bonds, wherein the uPAR-targeting peptide conjugate may be used as fluorescence probe in real time optical imaging and delineation of cancer tumors or metastases during surgery.

Abstract: The present invention describes a receptor-targeting conjugate comprising a fluorophore; a molecule, e.g. a peptide, binding to the receptor; and —a linker group which covalently links the fluorophore to the molecule binding to the receptor, wherein the conjugate is adapted to be administered intravenously into a human or animal body, and provide an effective pharmacokinetic profile with reference to inter alia receptor binding affinity and removal from plasma.

Abstract: Novel 18F-labelled tetrazines are provided which are highly reactive to be effective in vivo, suitable for pretargeted positron emission tomography (PET) and accessible in radiochemical yields (RCYs) which allow access to 18F-labeled tetrazines for clinical applications. The 18F-labelled tetrazines are developed using a Cu-mediated click indirect labelling approach. Only a subset of compounds appeared to be suitable for clinical pretargeted imaging strategies, and a particular compound which includes the use of an 18F-labelled azide synthon having an azide structure with glucose as the linker and a triazole moiety within the linker, appears to be highly suited for clinical pretargeted imaging purposes.

Abstract: There is provided a positron-emitting radionuclide labelled peptide for non-invasive PET imaging of the Urokinase-type Plasminogen Activator Receptor (uPAR) in humans. More specifically the invention relates to human uPAR PET imaging of any solid cancer disease for diagnosis, staging, treatment monitoring and especially as an imaging biomarker for predicting prognosis, progression and recurrence.

Abstract: There is provided a positron-emitting radionuclide labelled peptide for non-invasive PET imaging of the Urokinase-type Plasminogen Activator Receptor (uPAR) in humans. More specifically the invention relates to human uPAR PET imaging of any solid cancer disease for diagnosis, staging, treatment monitoring and especially as an imaging biomarker for predicting prognosis, progression and recurrence.

Abstract: The present invention relates to novel tetrazine compounds of formula I, wherein one of R1-R5 is 18F, for use in pretargeted in vivo imaging. The compounds are suitable for use in click chemistry, i.e. reactions that join a targeting molecule and a reporter molecule. The invention further relates to precursors to formula I, wherein one of R1-R5 is SnR3, B(OR)2, B(0H)2. Formula (I).

Abstract: There is provided a radiolabelled peptide-based compound for diagnostic imaging using positron emission tomography (PET). The compound may thus be used for diagnosis of malignant diseases. The compound is particularly useful for imaging of somatostatin overexpression in tumors, wherein the compound is capable of being imaged by PET when administered with a target dose in the range of 150-350 MBq, such as 150-250 MBq, preferable in the range of 191-210 MBq.

Abstract: There is provided a radiolabelled peptide-based compound for diagnostic imaging using positron emission tomography (PET). The compound may thus be used for diagnosis of malignant diseases. The compound is particularly useful for imaging of somatostatin overexpression in tumors, wherein the compound is capable of being imaged by PET when administered with a target dose in the range of 150-350 MBq, such as 150-250 MBq, preferable in the range of 191-210 MBq.