64Cu Treatment Planning and 67Cu Therapy with Radiolabelled SARTATE ([64Cu/67Cu]MeCOSAR-Octreotate) in Subjects with Unresectable Multifocal Meningioma - Initial Results for Human Imaging, Safety, Biodistribution and Radiation Dosimetry.

Aim: To report the use of copper-64 and copper-67 as a theranostic pair of radionuclides in human subjects. In addition, to measure whole organ dosimetry of copper-64 and copper-67 attached to the somatostatin analogue Octreotate using the sarcophagine MeCOSAR chelator ("SARTATE") in subjects with somatostatin receptor-expressing lesions confined to the cranium, thereby permitting normal organ dosimetry for the remainder of the body. Methods: Pre-treatment PET imaging studies were performed up to 24 hours after injection of [64Cu]Cu-SARTATE and normal organ dosimetry estimates were made using OLINDA/EXM. Subsequently the trial subjects with multifocal meningiomas were given therapeutic doses of [67Cu]Cu-SARTATE and imaged over a number of days using SPECT/CT. Results: Five subjects were initially recruited and imaged using PET/CT prior to treatment. Three of the subjects were subsequently administered four cycles each of [67Cu]Cu-SARTATE followed by multiple SPECT/CT imaging timepoints. No serious adverse events (SAEs) were observed and no adverse events led to withdrawal from the study or discontinuation from treatment. The mean Effective Dose estimated was 3.95 × 10-2 mSv/MBq for [64Cu]Cu-SARTATE and 7.62 × 10-2 mSv/MBq for [67Cu]Cu-SARTATE. The highest estimated organ dose was in spleen followed by kidneys, liver, adrenals and small intestine. The matched pairing was shown by PET and SPECT intra-subject imaging to have near identical targeting to tumours for guiding therapy, demonstrating a potentially accurate and precise theranostic product. Conclusion: Copper-64 and copper-67 show great promise as a theranostic pair of radionuclides. Further clinical studies will be required to examine the therapeutic dose required for [67Cu]Cu-SARTATE for various indications. In addition, the ability to use predictive copper-64 based dosimetry for treatment planning with copper-67 should be further explored.