title: Preparation of therapeutic dose of 177Lu-DOTA-TATE using a novel single vial freeze-dried kit: a comparison with 'in-situ' preparation at hospital radiopharmacy.
abstract: OBJECTIVE
  Patient dose of (177)Lu-DOTA-TATE, used for providing radiotherapeutic treatment to the patients suffering from cancers of neuroendocrine origin, could be prepared at the hospital radiopharmacy either 'in-situ' or by using freezedried kits. The objective of the present work is to formulate and evaluate a single vial freeze-dried DOTA-TATE kit, which is capable of producing up to 7.4 GBq (200 mCi) dose of (177)Lu-DOTA-TATE and to compare the two methodologies presently used for the preparation of the agent.
  
  
  METHODS
  Freeze-dried DOTA-TATE kits, comprising a lyophilized mixture of DOTA-TATE, gentisic acid and ammonium acetate, were prepared and used for the formulation of patient doses of (177)Lu-DOTA-TATE. The kits were subjected to detailed radiochemical evaluation and the shelf-life of the kits was determined. The pharmacokinetic behavior of the agent was studied in normal Wistar rats. These kits were utilized for treating the patients suffering from various types of neuroendocrine cancers.
  
  
  RESULTS
  The freeze-dried kits were used for the preparation of up to 7.4 GBq (200 mCi) therapeutic doses of (177)Lu- DOTA-TATE with a radiochemical purity of >99% and were found to have sufficiently long shelf-life. Biological studies carried out in normal Wistar rats exhibited no significant accumulation of activity in any of the vital organs/tissue except in kidneys and non-accumulated activity showed major renal clearance. Clinical studies carried out in cancer patients exhibited accumulation of activity in the cancerous lesions and metastatic sites.
  
  
  CONCLUSIONS
  The kit was useful for the convenient preparation of therapeutic dose of (177)Lu-DOTA-TATE, suitable for human administration. The use of kit is expected to reduce the batch failure and radiation exposure to the working personnel.
authors.forename: Tapas
authors.initials: T
authors.lastname: Das
authors.forename: Sharmila
authors.initials: S
authors.lastname: Banerjee
authors.forename: Ajit
authors.initials: A
authors.lastname: Shinto
authors.forename: K K
authors.initials: KK
authors.lastname: Kamaleshwaran
authors.affiliation: Isotope Applications and Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400 085, India. tdas@barc.gov.in.
authors.forename: H D
authors.initials: HD
authors.lastname: Sarma
mesh_terms: D000328:Adult; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005612:Freeze Drying; D006801:Humans; D008187:Lutetium / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000532:radiotherapy; D015282:Octreotide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011786:Quality Control; D011868:Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D051598:Whole Body Imaging
chemical_list: D009942:Organometallic Compounds; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D008187:Lutetium; C447941:lutetium Lu 177 dotatate; D015282:Octreotide