Applications for Theranostics

NuView is preparing to expand its portfolio for Theranostics applications using the NV-VPAC1™ peptide analog by pairing a diagnostic imaging positron emitter, Copper- 64 (Cu-64), with a beta-emitter, Copper-67 (Cu-67), a therapeutic cancer killing isotope. This paired Theranostics approach allows the physician to diagnose and localize the cancer, and subsequently visualize where the therapy is delivered, and enhance monitoring response to therapy.

Abstract

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Objectives: To examine the radiological properties of Next Generation Theranostics

Methods: Next generation theranostics can potentially offer improvements on both quality of diagnostic imaging using the PET isotope Cu-64 and therapeutic advantages using Cu-67 for a range of different tumor types. For the case of neuroendocrine tumors (NETS) in adults and neuroblastoma in children, an initial radiological comparisons is made with traditional, emerging, and future theranostic radiopharmaceuticals to examine: The suitability of the different radionuclides for imaging and therapy where comparisons of Cu-64 and Ga-68 for PET imaging and Cu-67 and Lu-177 for therapy using PRRT are made. The practicalities of handling theses radionuclides in a clinical setting where a T1/2 of 12.7 hours of Cu-64 impacts on radiochemistry, manufacture and logistics. The radiation safety parameters for the different radionuclides where a comparison using Annual Limits of Intake (ALIs) and external dose rates for Cu-64 to Ga-68 and Cu-67 to Lu-177 is made.

Results: Cu-64 for diagnostic PET imaging paired with Cu-67 for therapy provides: advantages for prospective dosimetry in PRRT; practical advantages in manufacture such as centralized GMP manufacture and distribution; and comparable and acceptable radiation safety to the current and popular theranostic isotopes.

Conclusion: The radiological properties of next generation theranostics based on Cu-64 (diagnostic) and Cu-67 (therapeutic) may offer significant advantages for a range of different tumor types. Research Support: N/A

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Abstract

The application of the beta particle-emitting nuclide 67Cu in radioimmunotherapy is reviewed. The production of the nuclide is outlined, and different production modes are discussed with an emphasis on cyclotron production. A short survey of copper chelators currently used for antibody labelling and their impact on the pharmacokinetics of 67Cu-labelled immunoconjugates is provided. Protocols for antibody labelling with 67Cu as well as quality control procedures for 67Cu-labelled antibodies are described. Preclinical data on the biological properties of 67Cu-labelled immunoconjugates are reported and discussed. 67Cu-labelled antibodies show higher and more persistent tumour uptake than their radioiodinated counterparts due to accumulation of labelled metabolites in tumour cells. Biodistribution of 67Cu-labelled antibody fragments has been improved by selection of negatively charged chelators and peptide linkers. Pharmacokinetic analysis of the accumulated dose in tumour and critical organs such as the kidney and liver indicates that, despite this improvement, intact 67Cu-labelled antibodies achieve higher tumour uptake and better therapeutic ratios than 67Cu-labelled antibody fragments and that they are at present the logical choice for clinical studies. Clinical studies using 67Cu-labelled antibodies in lymphoma, colon carcinoma and bladder cancer patients are reviewed. Some of the advantages over radioiodinated antibodies found in the preclinical work, such as higher tumour uptake and better tumour/blood ratios, have also been found with systemic application in lymphoma and colon carcinoma. However, in both lymphoma and colon carcinoma patients, the radiation dose to the liver has been found to be higher from 67Cu- than from 131I-labelled antibodies. The intravesical application of 67Cu-labelled antibody has been shown to be a promising approach for targetting cytotoxic radiation to superficial bladder tumours, without detectable systemic absorption. Given the favourable properties of 67Cu-labelled antibodies, it is the reliable availability of the 67Cu nuclide which is the limiting factor for their more widespread evaluation in radioimmunotherapy trials.

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