title: Post-therapeutic dosimetry of 177Lu-DKFZ-PSMA-617 in the treatment of patients with metastatic castration-resistant prostate cancer.
abstract: OBJECTIVE
  Lu-DKFZ-PSMA-617, a urea-based compound, binds to the extracellular domain of prostate-specific membrane antigen, thus providing an effective target for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Before its therapeutic use, it is necessary that the radiation dosimetry of this radiopharmaceutical be studied to determine the safe activity that can be administered in patients to prevent haematological, renal and liver toxicity. The present study thus aimed to assess the pharmacokinetics and dosimetry of Lu-DKFZ-PSMA-617 in CRPC patients.
  
  
  METHODS
  After obtaining ethical clearance from the institute ethics review board, we enrolled mCRPC patients who were positive on a Glu-NH-CO-NH-Lys-(Ahx)-[Ga(HBED-CC)] PET/CT scan. For kidney protection, a cocktail of lysine and arginine diluted in 2 litres of normal saline was infused, starting from 30 to 60 min before Lu-DKFZ-PSMA-617 infusion. The mean administered activity in the overall population was 2.52±1.3 GBq. For the purpose of dosimetry, each patient underwent nine planar whole-body scans along with blood and urine sample collection at 0.5, 3.5, 24, 48, 72, 96, 120, 144 and 168 h, respectively. SPECT/CT was performed to derive the volume of salivary glands (parotid and submandibular glands) and tumour. Dosimetric evaluation was carried out using the OLINDA/EXM 1.0 software.
  
  
  RESULTS
  A total of 26 mCRPC patients with a mean age of 66.30±9.95 years (range: 38-81 years) were recruited. Normal physiological uptake was observed in all the patients in the lacrimal glands, salivary glands (parotid glands and submandibular glands), liver, spleen, kidneys, intestines and urinary bladder. Organs with the highest absorbed doses were the salivary glands, followed by the kidneys, receiving 1.24±0.26 and 0.99±0.31 mGy/MBq, respectively. The mean absorbed doses to the liver, urinary bladder and red marrow were 0.36±0.10, 0.243±0.09 and 0.048±0.05 mGy/MBq, respectively. The mean whole-body dose was 0.016±0.003 mGy/MBq.
  
  
  CONCLUSIONS
  Lu-DKFZ-PSMA-617 therapy is a safe option in the treatment of mCRPC patients.
authors: Departments of aNuclear Medicine bMedical Oncology cUrology, All India Institute of Medical Sciences, New Delhi, India.
authors: Madhav P
authors: MP
authors: Yadav
authors: Sanjana
authors: S
authors: Ballal
authors: Madhavi
authors: M
authors: Tripathi
authors: Nishikant A
authors: NA
authors: Damle
authors: Ranjit K
authors: RK
authors: Sahoo
authors: Amlesh
authors: A
authors: Seth
authors: Chandrasekhar
authors: C
authors: Bal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000378:metabolism; D004151:Dipeptides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism; D006573:Heterocyclic Compounds, 1-Ring / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008187:Lutetium / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010455:Peptides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000072078:Positron Emission Tomography Computed Tomography; D017430:Prostate-Specific Antigen; D064129:Prostatic Neoplasms, Castration-Resistant / Q000000981:diagnostic imaging / Q000532:radiotherapy* / Q000556:secondary*; D011868:Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D051598:Whole Body Imaging; D014915:Whole-Body Counting
chemical_list: C000603664:177Lu-DKFZ-617; C000610110:Pluvicto; D000954:Antigens, Surface; D004151:Dipeptides; D006573:Heterocyclic Compounds, 1-Ring; D009942:Organometallic Compounds; D010455:Peptides; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D008187:Lutetium; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen