Copper-64 Dichloride as Theranostic Agent for Glioblastoma Multiforme: A Preclinical Study

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults with a median survival time less than one year. To date, there are only a limited number of effective agents available for GBM therapy and this does not seem to add much survival advantage over the conventional approach based on surgery and radiotherapy. Therefore, the development of novel therapeutic approaches to GBM is essential and those based on radionuclide therapy could be of significant clinical impact. Experimental evidence has clearly demonstrated that cancer cells have a particularly high fractional content of copper inside the nucleus compared to normal cells. This behavior can be conveniently exploited both for diagnosis and for delivering therapeutic payloads (theranostic) of the radionuclide copper-64 into the nucleus of cancerous cells by intravenous administration of its simplest chemical form as dichloride salt [64Cu]CuCl To evaluate the potential theranostic role of [64Cu]CuClin GBM, the present work reports results from a preclinical study carried out in a xenografted GBM tumor mouse model. Biodistribution data of this new agent were collected using a small-animal PET tomograph. Subsequently, groups of tumor implanted nude mice were treated with [64Cu]CuClto simulate single-and multiple-dose therapy protocols, and results were analyzed to estimate therapeutic efficacy

Theranostic in early detection of recurring prostate cancer: 64CuCl2

Aim: To evaluate the use of PET/CT with 64CuCl2 in recurring prostate cancer after surgery in patients with low PSA level (<2). Introduction: Previous works* demonstrated as 64CuCl2 is a PET probe in prostate cancer in mice with xenografts of prostate cancer.Moreover, it was described** in seven patients the role of 64CuCl2 PET/CT in staging of prostate cancer. Method: 32 Patients with low PSA level (<2) in recurring prostate post-surgical cancer were studied with 64CuCl2 PET/CT executed at 1, 3 and 24 h after injection of 200–400 MBq (medium activity 4 MBq/kg). A dosimetric analysis was done with manual VOI on various organs (Liver, Kidneys, Spleen, lumbar spine L4-L5 and Prostate as target). Coregistered imaging with CT to calculate VOIs, specific activity (Bq/ml) and SUVmax were executed. We analyzed time/activity curve with Olinda/EXM software to calculate absorbed dose. All patients had a control of PSA 10 days after PET/CT scan. Results: The PSA value was 1.1 ng/ml (0.4–1.9 ng/ml). All patients showed lesions with an uptake of 64CuCl2 with a ratio lesion/background grate than 10. The positive lesions (n=63) had a medium dimension of 5.2 mm (3–9 mm) in linfonodes (n=46), Prostatic lodge (n=13) and Bone (n=4). After 10 days all patients presented a reduction of PSA with a medium of 0.3 ng/ml (0.1–0.5). Sensibility 90%. Conclusion: PET/CT scan with 64CuCl2 is a high sensitivity method to detect early recurring prostate cancer after surgery. The possibility to see the lesions in early stage and in low dimensions (3–9 mm) opens a new possibility for theranostic application. The reduction value of PSA after 10 days could be related to the therapeutic effect of 64CuCl2. When the lesions are very small, a diagnostic dose could be also therapeutic. Further studies are necessary, but this could be a new approach in theranostic application