title: Dosimetry for (177)Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer.
abstract: OBJECTIVE
  Dosimetry is critical to achieve the optimal therapeutic effect of radioligand therapy (RLT) with limited side effects. Our aim was to perform image-based absorbed dose calculation for the new PSMA ligand (177)Lu-DKFZ-PSMA-617 in support of its use for the treatment of metastatic prostate cancer.
  
  
  METHODS
  Whole-body planar images and SPECT/CT images of the abdomen were acquired in five patients (mean age 68 years) for during two treatment cycles at approximately 1, 24, 48 and 72 h after administration of 3.6 GBq (range 3.4 to 3.9 GBq) (177)Lu-DKFZ-PSMA-617. Quantitative 3D SPECT OSEM reconstruction was performed with corrections for photon scatter, photon attenuation and detector blurring. A camera-specific calibration factor derived from phantom measurements was used for quantitation. Absorbed doses were calculated for various organs from the images using a combination of linear approximation, exponential fit, and target-specific S values, in accordance with the MIRD scheme. Absorbed doses to bone marrow were estimated from planar and SPECT images and with consideration of the blood sampling method according to the EANM guidelines.
  
  
  RESULTS
  The average (± SD) absorbed doses per cycle were 2.2 ± 0.6 Gy for the kidneys (0.6 Gy/GBq), 5.1 ± 1.8 Gy for the salivary glands (1.4 Gy/GBq), 0.4 ± 0.2 Gy for the liver (0.1 Gy/GBq), 0.4 ± 0.1 Gy for the spleen (0.1 Gy/GBq), and 44 ± 19 mGy for the bone marrow (0.012 Gy/GBq). The organ absorbed doses did not differ significantly between cycles. The critical absorbed dose reported for the kidneys (23 Gy) was not reached in any patient. At 24 h there was increased uptake in the colon with 50 - 70 % overlap to the kidneys on planar images. Absorbed doses for tumour lesions ranged between 1.2 and 47.5 Gy (13.1 Gy/GBq) per cycle.
  
  
  CONCLUSIONS
  The salivary glands and kidneys showed high, but not critical, absorbed doses after RLT with (177)Lu-DKFZ-PSMA-617. We suggest that (177)Lu-DKFZ-PSMA-617 is suitable for radiotherapy, offering tumour-to-kidney ratios comparable to those with RLT agents currently available for the treatment of neuroendocrine tumours. Our dosimetry results suggest that (177)Lu-DKFZ-PSMA-617 treatment with higher activities and more cycles is possible without the risk of damaging the kidneys.
authors: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377, Munich, Germany.
authors: Andreas
authors: A
authors: Delker
authors: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377, Munich, Germany.
authors: Wolfgang Peter
authors: WP
authors: Fendler
authors: Department for Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Germany.
authors: Clemens
authors: C
authors: Kratochwil
authors: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377, Munich, Germany.
authors: Anika
authors: A
authors: Brunegraf
authors: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377, Munich, Germany.
authors: Astrid
authors: A
authors: Gosewisch
authors: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377, Munich, Germany.
authors: Franz Josef
authors: FJ
authors: Gildehaus
authors: Department of Urology, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors: Stefan
authors: S
authors: Tritschler
authors: Department of Urology, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors: Christian Georg
authors: CG
authors: Stief
authors: Division of Radiopharmaceutical Chemistry, German Cancer Research Center (dkfz), Heidelberg, Germany.
authors: Klaus
authors: K
authors: Kopka
authors: Department for Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Germany.
authors: Uwe
authors: U
authors: Haberkorn
authors: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377, Munich, Germany.
authors: Peter
authors: P
authors: Bartenstein
authors: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377, Munich, Germany. Guido.Boening@med.uni-muenchen.de.
authors: Guido
authors: G
authors: Böning
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000378:metabolism*; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009942:Organometallic Compounds / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use*; D010455:Peptides / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use*
chemical_list: C000603664:177Lu-DKFZ-617; D000954:Antigens, Surface; D009942:Organometallic Compounds; D010455:Peptides; D019275:Radiopharmaceuticals; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II
keywords: Dosimetry; Lutetium-177; PSMA; Prostate cancer; Radioligand radiation therapy; mCRPC