title: Pre-therapeutic dosimetry of normal organs and tissues of (177)Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer.
abstract: OBJECTIVE
  (177)Lu-617-prostate-specific membrane antigen (PSMA) ligand seems to be a promising tracer for radionuclide therapy of progressive prostate cancer. However, there are no published data regarding the radiation dose given to the normal tissues. The aim of the present study was to estimate the pretreatment radiation doses in patients who will undergo radiometabolic therapy using a tracer amount of (177)Lu-labeled PSMA ligand.
  
  
  METHODS
  The study included seven patients with progressive prostate cancer with a mean age of 63.9 ± 3.9 years. All patients had prior PSMA positron emission tomography (PET) imaging and had intense tracer uptake at the lesions. The injected (177)Lu-PSMA-617 activity ranged from 185 to 210 MBq with a mean of 192.6 ± 11.0 MBq. To evaluate bone marrow absorbed dose 2-cc blood samples were withdrawn in short variable times (3, 15, 30, 60, and 180 min and 24, 48, and 120 h) after injection. Whole-body images were obtained at 4, 24, 48, and 120 h post-injection (p.i.). The geometric mean of anterior and posterior counts was determined through region of interest (ROI) analysis. Attenuation correction was applied using PSMA PET/CT images. The OLINDA/EXM dosimetry program was used for curve fitting, residence time calculation, and absorbed dose calculations.
  
  
  RESULTS
  The calculated radiation-absorbed doses for each organ showed substantial variation. The highest radiation estimated doses were calculated for parotid glands and kidneys. Calculated radiation-absorbed doses per megabecquerel were 1.17 ± 0.31 mGy for parotid glands and 0.88 ± 0.40 mGy for kidneys. The radiation dose given to the bone marrow was significantly lower than those of kidney and parotid glands (p < 0.05). The calculated radiation dose to bone marrow was 0.03 ± 0.01 mGy/MBq.
  
  
  CONCLUSIONS
  Our first results suggested that (177)Lu-PSMA-617 therapy seems to be a safe method. The dose-limiting organ seems to be the parotid glands rather than kidneys and bone marrow. The lesion radiation doses are within acceptable ranges; however, there is a substantial individual variance so patient dosimetry seems to be mandatory.
authors.affiliation: Department of Nuclear Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey. lkabasakal@tsnm.org.
authors.forename: Levent
authors.initials: L
authors.lastname: Kabasakal
authors.affiliation: Department of Nuclear Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Mohammad
authors.initials: M
authors.lastname: AbuQbeitah
authors.affiliation: Department of Nuclear Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Aslan
authors.initials: A
authors.lastname: Aygün
authors.affiliation: Department of Nuclear Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Nami
authors.initials: N
authors.lastname: Yeyin
authors.affiliation: Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Meltem
authors.initials: M
authors.lastname: Ocak
authors.affiliation: Department of Nuclear Medicine, Sisli Etfal Training and Research Hospital, Istanbul, Turkey.
authors.forename: Emre
authors.initials: E
authors.lastname: Demirci
authors.affiliation: Department of Nuclear Medicine, Yeditepe University Medical Faculty, Istanbul, Turkey.
authors.forename: Turkay
authors.initials: T
authors.lastname: Toklu
mesh_terms: D000368:Aged; D000954:Antigens, Surface; D001853:Bone Marrow / Q000528:radiation effects; D004151:Dipeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D043425:Glutamate Carboxypeptidase II / Q000037:antagonists & inhibitors*; D006573:Heterocyclic Compounds, 1-Ring / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007668:Kidney / Q000528:radiation effects; D008187:Lutetium; D008297:Male; D008875:Middle Aged; D058958:Organs at Risk / Q000528:radiation effects; D010306:Parotid Gland / Q000528:radiation effects; D017430:Prostate-Specific Antigen; D064129:Prostatic Neoplasms, Castration-Resistant / Q000532:radiotherapy*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011879:Radiotherapy Dosage
chemical_list: C000610110:Pluvicto; D000954:Antigens, Surface; D004151:Dipeptides; D006573:Heterocyclic Compounds, 1-Ring; D019275:Radiopharmaceuticals; D008187:Lutetium; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen
keywords: Castration resistant; Lu-177-PSMA; PSMA; Prostate cancer; Prostate specific membrane antigen; Radiometabolic therapy; Radionuclide treatment