title: Clinical68Ga-PET: Is radiosynthesis module an absolute necessity?
abstract: BACKGROUND
  The commercially available68Ge/68Ga generators are generally used in clinical context in conjunction with automated or semi-automated modules for the syntheses of68Ga radiopharmaceuticals. It is desirable to develop strategies for the formulation of68Ga-radiopharmaceuticals without use of such expensive modules in order to make68Ga-based clinical positron emission tomography (PET) more popular and affordable worldwide.
  
  
  METHODS
  An organic matrix based68Ge/68Ga generator was used for preparation of clinically relevant doses of four different68Ga-based radiopharmaceuticals, namely68Ga-DOTA-NOC,68Ga-NODAGA-RGD2,68Ga-PSMA-11 and68Ga-BPAMD. Detailed performance evaluation of the generator was carried out over the period of 9months. The radiolabeling conditions were optimized in a hospital radiopharmacy directly utilizing68Ga eluted from the generator without use of any synthesis module. Quality control tests of the radiopharmaceuticals were carried out to assess their suitability for clinical use. The clinical utility of the synthesized radiopharmaceuticals was ascertained by performing PET scans in human patients.
  
  
  RESULTS
  During the period of evaluation,68Ga could be obtained from the generator in 4mL of 0.05M HCl with 60-85% elution yield and >99.99% radionuclidic purity. While directly using68Ga eluted from the generator, the68Ga-based radiopharmaceuticals could be prepared with >95% radiochemical purity and they met all the requirements for clinical administration. The clinical efficacy of the radiopharmaceuticals synthesized was established by PET scans in human patients. The performance of the generator remained consistent over the 9-month period and >100 clinical doses of different radiopharmaceuticals were prepared with excellent reproducibility and clinical effectiveness.
  
  
  CONCLUSIONS
  The promising results obtained in this study would make68Ga-radiopharmacy more practical and cost effective in clinical context. To the best of our knowledge, this is the first report on the clinical scale syntheses and utilization of68Ga-based radiopharmaceuticals without using any synthesis module.
authors.affiliation: Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India. Electronic address: rubelc@barc.gov.in.
authors.forename: Rubel
authors.initials: R
authors.lastname: Chakravarty
authors.affiliation: Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India. Electronic address: sudipta@barc.gov.in.
authors.forename: Sudipta
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Nuclear Medicine and PET Services, Comprehensive Cancer Care Centre, Kovai Medical Centre and Hospital, Coimbatore - 641 014, India.
authors.forename: E R
authors.initials: ER
authors.lastname: Radhakrishnan
authors.affiliation: Nuclear Medicine and PET Services, Comprehensive Cancer Care Centre, Kovai Medical Centre and Hospital, Coimbatore - 641 014, India.
authors.forename: Koramadai
authors.initials: K
authors.lastname: Kamaleshwaran
authors.affiliation: Nuclear Medicine and PET Services, Comprehensive Cancer Care Centre, Kovai Medical Centre and Hospital, Coimbatore - 641 014, India.
authors.forename: Ajit
authors.initials: A
authors.lastname: Shinto
authors.affiliation: Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Dash
mesh_terms: D005260:Female; D005710:Gallium Radioisotopes / Q000737:chemistry; D005857:Germanium / Q000737:chemistry; D006761:Hospitals; D006801:Humans; D007553:Isotope Labeling; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011854:Radiochemistry / Q000295:instrumentation / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry; D012449:Safety
chemical_list: D005710:Gallium Radioisotopes; D019275:Radiopharmaceuticals; D005857:Germanium
keywords: (68)Ga-BPAMD; (68)Ga-DKFZ-PSMA-11; (68)Ga-DOTANOC; (68)Ga-NODAGA-RGD(2); (68)Ge/(68)Ga generator; Pet