64Cu Treatment Planning and 67Cu Therapy with Radiolabeled [64Cu/67Cu]MeCOSar-Octreotate in Subjects with Unresectable Multifocal Meningioma: Initial Results for Human Imaging, Safety, Biodistribution, and Radiation Dosimetry

Dale L Bailey; Kathy P Willowson; Matthew Harris; Colin Biggin; Alireza Aslani; Nigel A Lengkeek; Jon Stoner; M Enid Eslick; Harry Marquis; Michelle Parker; Paul J Roach; Geoffrey P Schembri

doi:10.2967/jnumed.122.264586

⁶⁴Cu Treatment Planning and ⁶⁷Cu Therapy with Radiolabeled [⁶⁴Cu/⁶⁷Cu]MeCOSar-Octreotate in Subjects with Unresectable Multifocal Meningioma: Initial Results for Human Imaging, Safety, Biodistribution, and Radiation Dosimetry

J Nucl Med. 2023 May;64(5):704-710. doi: 10.2967/jnumed.122.264586. Epub 2022 Dec 2.

Authors

Dale L Bailey^{1

2

3}, Kathy P Willowson^{4

5}, Matthew Harris⁶, Colin Biggin⁶, Alireza Aslani^{4

2}, Nigel A Lengkeek⁷, Jon Stoner⁸, M Enid Eslick⁴, Harry Marquis^{3

5}, Michelle Parker⁶, Paul J Roach^{4

2}, Geoffrey P Schembri^{4

2}

Affiliations

¹ Department of Nuclear Medicine, Royal North Shore Hospital, Sydney, New South Wales, Australia; dale.bailey@sydney.edu.au.
² Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
³ Sydney Vital Translational Cancer Research Centre, Sydney, New South Wales, Australia.
⁴ Department of Nuclear Medicine, Royal North Shore Hospital, Sydney, New South Wales, Australia.
⁵ Institute of Medical Physics, University of Sydney, Sydney, New South Wales, Australia.
⁶ Clarity Pharmaceuticals, Sydney, New South Wales, Australia.
⁷ ANSTO Biosciences, Sydney, New South Wales, Australia; and.
⁸ Idaho Accelerator Center, Idaho State University, Pocatello, Idaho.

PMID: 36460344
DOI: 10.2967/jnumed.122.264586

Abstract

Our aim was to report the use of ⁶⁴Cu and ⁶⁷Cu as a theranostic pair of radionuclides in human subjects. An additional aim was to measure whole-organ dosimetry of ⁶⁴Cu and ⁶⁷Cu attached to the somatostatin analog 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: Pretreatment PET imaging studies were performed up to 24 h after injection of [⁶⁴Cu]Cu-SARTATE, and normal-organ dosimetry was estimated using OLINDA/EXM. Subsequently, the trial subjects with multifocal meningiomas were given therapeutic doses of [⁶⁷Cu]Cu-SARTATE and imaged over several days using SPECT/CT. Results: Five subjects were initially recruited and imaged using PET/CT before treatment. Three of the subjects were subsequently administered 4 cycles each of [⁶⁷Cu]Cu-SARTATE followed by multiple SPECT/CT imaging time points. No serious adverse events were observed, and no adverse events led to withdrawal from the study or discontinuation from treatment. The estimated mean effective dose 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 intrasubject imaging to have nearly identical targeting to tumors for guiding therapy, demonstrating a potentially accurate and precise theranostic product. Conclusion: ⁶⁴Cu and ⁶⁷Cu 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 ⁶⁴Cu-based dosimetry for treatment planning with ⁶⁷Cu should be further explored.

Trial registration: ClinicalTrials.gov NCT03936426.

Keywords: copper radionuclides; dosimetry; meningioma; radionuclide therapy; safety; theranostics.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Humans
Meningeal Neoplasms*
Meningioma* / diagnostic imaging
Meningioma* / radiotherapy
Positron Emission Tomography Computed Tomography / methods
Radioisotopes
Radiometry
Radiopharmaceuticals / therapeutic use
Tissue Distribution

Substances

Radioisotopes
Radiopharmaceuticals

Associated data

ClinicalTrials.gov/NCT03936426