title: The68Ga/177Lu theragnostic concept in PSMA targeting of castration-resistant prostate cancer: correlation of SUVmaxvalues and absorbed dose estimates.
abstract: BACKGROUND
  A targeted theragnostic approach based on increased expression of prostate-specific membrane antigen (PSMA) on PC cells is an attractive treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC).
  
  
  METHODS
  Ten consecutive mCRPC patients were selected for177Lu-PSMA617 therapy on the basis of PSMA-targeted68Ga-PSMA-HBED-CC PET/CT diagnosis showing extensive and progressive tumour load. Following dosimetry along with the first therapy cycle restaging (68Ga-PSMA-HBED-CC and18F-NaF PET/CT) was performed after 2 and 3 therapy cycles (each 6.1 ± 0.3 GBq, range 5.4-6.5 GBq) given intravenously over 30 minutes, 9 ± 1 weeks apart. PET/CT scans were compared to177Lu-PSMA617 24-hour whole-body scans and contrast-enhanced dual-phase CT. Detailed comparison of SUVmax values and absorbed tumour doses was performed.
  
  
  RESULTS
  177Lu-PSMA617 dosimetry indicated high tumour doses for skeletal (3.4 ± 1.9 Gy/GBq; range 1.1-7.2 Gy/GBq), lymph node (2.6 ± 0.4 Gy/GBq; range 2.3-2.9 Gy/GBq) as well as liver (2.4 ± 0.8 Gy/GBq; range 1.7-3.3 Gy/GBq) metastases whereas the dose for tissues/organs was acceptable in all patients for an intention-to-treat activity of 18 ± 0.3 GBq. Three patients showed partial remission, three mixed response, one stable and three progressive disease. Decreased177Lu-PSMA617 and68Ga-PSMA-HBED-CC uptake (mean SUVmax values 20.2 before and 15.0 after 2 cycles and 11.5 after 3 cycles, p < 0.05) was found in 41/54 skeletal lesions, 12/13 lymph node metastases, 3/5 visceral metastases and 4/4 primary PC lesions.
  
  
  CONCLUSIONS
  Due to substantial individual variance, dosimetry is mandatory for a patient-specific approach following177Lu-PSMA617 therapy. Higher activities and/or shorter treatment intervals should be applied in a larger prospective study.
authors.affiliation: Department of Nuclear Medicine, Medical University Innsbruck, Anichstraße 35, A-6020, Innsbruck, Austria.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Scarpa
authors.affiliation: Department of Nuclear Medicine, Medical University Innsbruck, Anichstraße 35, A-6020, Innsbruck, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Buxbaum
authors.affiliation: Department of Nuclear Medicine, Medical University Innsbruck, Anichstraße 35, A-6020, Innsbruck, Austria.
authors.forename: Dorota
authors.initials: D
authors.lastname: Kendler
authors.affiliation: Department of Nuclear Medicine, Medical University Innsbruck, Anichstraße 35, A-6020, Innsbruck, Austria.|Department of Radiotherapy / Radiation Oncology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Fink
authors.affiliation: Department of Urology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Bektic
authors.affiliation: Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Leonhard
authors.initials: L
authors.lastname: Gruber
authors.affiliation: Department of Nuclear Medicine, Medical University Innsbruck, Anichstraße 35, A-6020, Innsbruck, Austria.
authors.forename: Clemens
authors.initials: C
authors.lastname: Decristoforo
authors.affiliation: Department of Nuclear Medicine, Medical University Innsbruck, Anichstraße 35, A-6020, Innsbruck, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Uprimny
authors.affiliation: Department of Radiotherapy / Radiation Oncology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Lukas
authors.affiliation: Department of Urology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Horninger
authors.affiliation: Department of Nuclear Medicine, Medical University Innsbruck, Anichstraße 35, A-6020, Innsbruck, Austria. irene.virgolini@i-med.ac.at.
authors.forename: Irene
authors.initials: I
authors.lastname: Virgolini
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000378:metabolism*; D004492:Edetic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D005710:Gallium Radioisotopes; D015972:Gene Expression Regulation, Neoplastic; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism*; D006801:Humans; D008187:Lutetium / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D000072078:Positron Emission Tomography Computed Tomography; D064129:Prostatic Neoplasms, Castration-Resistant / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D011829:Radiation Dosage; D011879:Radiotherapy Dosage; D012449:Safety; D016896:Treatment Outcome
chemical_list: D000954:Antigens, Surface; D005710:Gallium Radioisotopes; C075313:N,N'-bis(2-hydroxy-5-(ethylene-beta-carboxy)benzyl)ethylenediamine N,N'-diacetic acid; D008187:Lutetium; D004492:Edetic Acid; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II
keywords: 18F-NaF-PET; 68Ga/177 Lu-PSMA-targeted theragnostic concept; Dosimetry; Prostate cancer