Theragnostic method for cancer patients

Abstract

A theragnostic method is here described for treating a subject affected by a neoplasia by administering in both the diagnostic and therapeutic steps the same radioisotope, which is a 64 Cu ++ salt. Such method comprises a diagnostic step to select a subject, in which there is 64 Cu ++ cellular uptake. In case there is no uptake, the treatment is not advisable. In case there is copper uptake from cancer lesions, this has a predictive value of response to treatment. If the subject is selected for the treatment, the method further comprises a step of treating cancer in said subject by administering a therapeutically effective amount of the same 64 Cu ++ salt.

1 . A method for treating a neoplasm in a human patient in need thereof, said method comprising:
 a) administering for diagnostic purpose to said patient a diagnostically effective amount of a radiopharmaceutical composition comprising as the active ingredient copper-64 in ionic form ( 64 Cu ++ ), in combination with suitable excipients, and/or diluents at a radioconcentration of 2,775 MBq/ml at calibration time;   b) acquiring an image by PET/MRI or PET/CT of said patient, to evidence any copper-64 uptake by neoplastic cells of the cancer lesions;   c) in case of evidence of copper-64 uptake by neoplastic cells, subjecting the patient to a treatment cycle by administering for therapeutic purpose to said patient a therapeutically effective amount of a radiopharmaceutical composition comprising as active ingredient copper-64 in ionic form ( 64 Cu ++ ), in combination with suitable excipients, and/or diluents, at a radioconcentration of 2,775 MBq/ml at calibration time.   
     
     
         2 . The method of  claim 1 , which is preceded by the following steps:
 i) collecting a blood sample from the human patient;   ii) detecting the content of chemical copper in such sample;   wherein step (c) is practiced only if serum copper level detected in the sample are over 150 μg/dL.   
     
     
         3 . The method of  claim 1 , wherein the human patient is female or male. 
     
     
         4 . The method of  claim 1 , wherein the human patient is a child or an adult. 
     
     
         5 . The method of  claim 1 , wherein step (b) is performed from 1 to 4 hours after step (a). 
     
     
         6 . The method of  claim 1 , wherein the dose administered in step (a) is from 5.3 MBq/kg and 13 MBq/kg. 
     
     
         7 . The method of  claim 1 , wherein the dose administered in step (c) is from 13 MBq/kg and 105 MBq/kg. 
     
     
         8 . The method of  claim 1 , wherein step (c) is repeated for 1 to 7 times per each treatment cycle. 
     
     
         9 . The method of  claim 1 , wherein step (b) is repeated at least once during the treatment cycle to monitor response to treatment. 
     
     
         10 . The method of  claim 1 , wherein the frequency of administration is from 1 to 3 times per week. 
     
     
         11 . The method of  claim 1 , wherein for each treatment cycle the dosage regimen comprises administering to the human patient-an increasing dose starting from the initial therapeutic dose (X 1 ) as follow: 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   1st dose 
                   X 1  MBq 
                 
                     
                   2nd dose 
                   X 2  = (X 1  + 33% of X 1 ) MBq 
                 
                     
                   3rd dose 
                   X 3  = (X 2  + 25% of X 1 ) MBq 
                 
                     
                   4th dose 
                   X 4  = (X 3  + 20% of X 1 ) MBq 
                 
                     
                   5th dose 
                   X 5  = (X 4  + 17% of X 1 ) MBq 
                 
                     
                   6th dose 
                   X 6  = (X 5  + 14% of X 1 ) MBq 
                 
                     
                   7th dose 
                   X 7  = (X 6  + 11% of X 1 ) MBq 
                 
                     
                     
                 
             
                
               
               
                
                
                
                
                
                
                
                
               
            
           
         
         or a fixed dose of the radiopharmaceutical composition. 
       
     
     
         12 . The method of  claim 1 , wherein for each treatment cycle the dosage regimen comprises the following administrations to an adult patient: Pt dose=1,850 MBq, 2 nd  dose=2,460MBq, 3rd dose=2,922 MBq, 4 th  dose=3,292 MBq, 5 th  dose=3,606 MBq, 6 th  dose=3,865 MBq, 7 th  dose=4,068 MBq, where the total activity administered is equal to 22,063 MBq per cycle. 
     
     
         13 . The method of  claim 1 , wherein for each treatment cycle the dosage regimen comprises the following administrations to an adult patient: Pt dose=4,810 MBq, 2 nd  dose=4,810 MBq, 3rd dose=4,810 MBq, 4 th  dose=4,810 MBq, 5 th  dose=4,810 MBq, 6 th  dose=4,810MBq, 7 th  dose=4,810MBq, where the total activity administered is equal to 33,670 MBq per cycle. 
     
     
         14 . The method of  claim 1 , wherein the PET imaging in step (b) is evaluated to evidence any uptake of  64 CuCl 2  by neoplastic cells of the cancer lesions of the patient through the determination of a target to background ratio (TBR), wherein a TBR value equal or higher than 5 is considered as evidencing an uptake of  64 CuCl 2 . 
     
     
         15 . The method of  claim 1 , which is repeated on said human patient at least 30 days after ending all the treatment cycles. 
     
     
         16 . A radiopharmaceutical composition comprising as the active ingredient copper-64 in ionic form, ( 64 Cu ++ ), in combination with suitable excipients, and/or diluents in a saline solution at a radioconcentration of 2,775 MBq/ml at calibration time. 
     
     
         17 . The radiopharmaceutical composition of  claim 16 , having a specific activity 10.000 MBq of  64 Cu/micrograms of copper. 
     
     
         18 . The radiopharmaceutical composition of  claim 16 , further comprising counter-ions present in the solution, said counter-ions being selected from the group consisting of chloride, acetate and citrate ions. 
     
     
         19 . The radiopharmaceutical composition of  claim 16 , comprising 5% of  64 CuCl 2 , 2% acetate buffer solution, 10-93% NaCl, 0,9%. 
     
     
         20 . The radiopharmaceutical composition of  claim 16 , comprising 8% of  64 Cu(OAc) 2 , 4% of acetate buffer solution, 12-88% of water for injection (WFI) and 1% of an antioxidant. 
     
     
         21 . The radiopharmaceutical composition of  claim 16 , having a pH suitable for direct injection, said pH having a value between 4-8.