title: Radiation Dosimetry for177Lu-PSMA I&T in Metastatic Castration-Resistant Prostate Cancer: Absorbed Dose in Normal Organs and Tumor Lesions.
abstract: Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy is increasingly used in metastatic castration-resistant prostate cancer. We aimed to estimate the absorbed doses for normal organs and tumor lesions using177Lu-PSMA I&T (I&T is imaging and therapy) in patients undergoing up to 4 cycles of radioligand therapy. Results were compared with pretherapeutic Glu-NH-CO-NH-Lys-(Ahx)-[68Ga(HBEDCC)] (68Ga-PSMA-HBED-CC) PET.Methods:A total of 34 cycles in 18 patients were analyzed retrospectively. In 15 patients the first, in 9 the second, in 5 the third, and in 5 the fourth cycle was analyzed, respectively. Whole-body scintigraphy was performed at least between 30-120 min, 24 h, and 6-8 d after administration. Regions of interest covering the whole body, organs, and up to 4 tumor lesions were drawn. Organ and tumor masses were derived from pretherapeutic68Ga-PSMA-HBED-CC PET/CT. Absorbed doses for individual cycles were calculated using OLINDA/EXM. SUVs from pretherapeutic PET were compared with absorbed doses and with change of SUV.Results:The mean whole-body effective dose for all cycles was 0.06 ± 0.03 Sv/GBq. The mean absorbed organ doses were 0.72 ± 0.21 Gy/GBq for the kidneys; 0.12 ± 0.06 Gy/GBq for the liver; and 0.55 ± 0.14 Gy/GBq for the parotid, 0.64 ± 0.40 Gy/GBq for the submandibular, and 3.8 ± 1.4 Gy/GBq for the lacrimal glands. Absorbed organ doses were relatively constant among the 4 different cycles. Tumor lesions received a mean absorbed dose per cycle of 3.2 ± 2.6 Gy/GBq (range, 0.22-12 Gy/GBq). Doses to tumor lesions gradually decreased, with 3.5 ± 2.9 Gy/GBq for the first, 3.3 ± 2.5 Gy/GBq for the second, 2.7 ± 2.3 Gy/GBq for the third, and 2.4 ± 2.2 Gy/GBq for the fourth cycle. SUVs of pretherapeutic PET moderately correlated with absorbed dose (r= 0.44,P< 0.001 for SUVmax;r= 0.43,P< 0.001 for SUVmean) and moderately correlated with the change of SUV (r= 0.478,P< 0.001 for SUVmax, andr= 0.50,P< 0.001 for SUVmean).Conclusion:Organ- and tumor-absorbed doses for177Lu-PSMA I&T are comparable to recent reports and complement these with information on an excellent correlation between the 4 therapy cycles. With the kidneys representing the critical organ, a cumulative activity of 40 GBq of177Lu-PSMA I&T appears to be safe and justifiable. The correlation between pretherapeutic SUV and absorbed tumor dose emphasizes the need for PSMA-ligand PET imaging for patient selection.
authors.affiliation: Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.|Department of Nuclear Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Shozo
authors.initials: S
authors.lastname: Okamoto
authors.affiliation: Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Thieme
authors.affiliation: Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Jakob
authors.initials: J
authors.lastname: Allmann
authors.affiliation: Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Calogero
authors.initials: C
authors.lastname: D'Alessandria
authors.affiliation: Department of Urology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Maurer
authors.affiliation: Department of Urology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Margitta
authors.initials: M
authors.lastname: Retz
authors.affiliation: Department of Urology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Tauber
authors.affiliation: Department of Urology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Matthias M
authors.initials: MM
authors.lastname: Heck
authors.affiliation: Chair of Pharmaceutical Radiochemistry, Technical University of Munich, Munich, Germany; and.
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Wester
authors.affiliation: Department of Nuclear Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Nagara
authors.initials: N
authors.lastname: Tamaki
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: Wolfgang P
authors.initials: WP
authors.lastname: Fendler
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: Ken
authors.initials: K
authors.lastname: Herrmann
authors.affiliation: Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Christian H
authors.initials: CH
authors.lastname: Pfob
authors.affiliation: Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Klemens
authors.initials: K
authors.lastname: Scheidhauer
authors.affiliation: Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
authors.affiliation: Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Ziegler
authors.affiliation: Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany matthias.eiber@tum.de.|Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: Matthias
authors.initials: M
authors.lastname: Eiber
mesh_terms: D065638:Absorption, Radiation; D000368:Aged; D004151:Dipeptides / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006573:Heterocyclic Compounds, 1-Ring / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006801:Humans; D008187:Lutetium; D008297:Male; D008657:Metabolic Clearance Rate; D009362:Neoplasm Metastasis; D059351:Organ Sparing Treatments / Q000379:methods; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods*; D017430:Prostate-Specific Antigen; D064129:Prostatic Neoplasms, Castration-Resistant / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D014018:Tissue Distribution; D016896:Treatment Outcome; D014915:Whole-Body Counting
chemical_list: C000610110:Pluvicto; D004151:Dipeptides; D006573:Heterocyclic Compounds, 1-Ring; D019275:Radiopharmaceuticals; D008187:Lutetium; D017430:Prostate-Specific Antigen
keywords: PSMA I&T; dosimetry; prostate cancer; radioligand therapy; response