ABSTRACT
In vivo pharmacokinetic analysis of [Sc]Sc-PSMA-617 was used to determine the normal organ-absorbed doses that may result from therapeutic activity of [Lu]Lu-PSMA-617 and to predict the maximum permissible activity of [Lu]Lu-PSMA-617 for patients with metastatic castration-resistant prostate carcinoma. METHODS: Pharmacokinetics of [Sc]Sc-PSMA-617 was evaluated in 5 patients with metastatic castration-resistant prostate carcinoma using dynamic PET/CT, followed by 3 static PET/CT acquisitions and blood sample collection over 19.5 hours, as well as urine sample collection at 2 time points. Total activity measured in source organs by PET imaging, as well as counts per milliliter measured in blood and urine samples, was decay corrected back to the time of injection using the half-life of Sc. Afterward, forward decay correction using the half-life of Lu was performed, extrapolating the pharmacokinetics of [Sc]Sc-PSMA-617 to that of [Lu]Lu-PSMA-617. Source organs residence times and organ-absorbed doses for [Lu]Lu-PSMA-617 were calculated using OLINDA/EXM software. Bone marrow self-dose was determined with indirect blood-based method, and urinary bladder contents residence time was estimated by trapezoidal approximation. The maximum permissible activity of [Lu]Lu-PSMA-617 was calculated for each patient considering external beam radiotherapy toxicity limits for radiation absorbed doses to kidneys, bone marrow, salivary glands, and whole body. RESULTS: The predicted mean organ-absorbed doses were highest in the kidneys (0.44 mSv/MBq), followed by the salivary glands (0.23 mSv/MBq). The maximum permissible activity was highly variable among patients; limited by whole body-absorbed dose (1 patient), marrow-absorbed dose (1 patient), and kidney-absorbed dose (3 patients). CONCLUSIONS: [Sc]Sc-PSMA-617 PET/CT imaging is feasible and allows theoretical extrapolation of the pharmacokinetics of [Sc]Sc-PSMA-617 to that of [Lu]Lu-PSMA-617, with the intent of predicting normal organ-absorbed doses and maximum permissible activity in patients scheduled for therapy with [Lu]Lu-PSMA-617.
Subject(s)
Carcinoma/radiotherapy , Dipeptides/pharmacokinetics , Heterocyclic Compounds, 1-Ring/pharmacokinetics , Organometallic Compounds/pharmacokinetics , Positron Emission Tomography Computed Tomography/methods , Prostatic Neoplasms, Castration-Resistant/radiotherapy , Radiation Dosage , Radiopharmaceuticals/pharmacokinetics , Radiotherapy Planning, Computer-Assisted/methods , Aged , Carcinoma/diagnostic imaging , Carcinoma/pathology , Dipeptides/therapeutic use , Heterocyclic Compounds, 1-Ring/therapeutic use , Humans , Lutetium , Male , Neoplasm Metastasis , Organometallic Compounds/therapeutic use , Prostate-Specific Antigen , Prostatic Neoplasms, Castration-Resistant/diagnostic imaging , Prostatic Neoplasms, Castration-Resistant/pathology , Radiopharmaceuticals/therapeutic use , Radiotherapy Dosage , ScandiumABSTRACT
AIM: [Sc]Sc-PSMA-617 with 3.9-hour half-life, in vitro and in vivo characteristics similar to [Lu]Lu-PSMA-617 and possibility of delayed imaging after 24 hours or later, implies it to be advantageous than [ Ga]Ga-PSMA-617 for pretherapeutic dosimetric assessment for [Lu]Lu-PSMA-617 in metastatic castration-resistant prostate carcinoma (mCRPC) patients. In this study, we investigated biodistribution and radiation exposure to normal organs with [Sc]Sc-PSMA-617 in mCRPC patients. METHODS: Five mCRPC patients (mean age, 69 years) enrolled for [Lu]Lu-PSMA-617 therapy were injected with 40-62 MBq [Sc]Sc-PSMA-617 intravenously; Siemens Biograph 2 PET/CT system was used to acquire dynamic PET data (30 minutes) in list mode over the abdomen, followed by the collection of static PET/CT images (skull to mid-thigh) at 45 minutes, 2 and approximately 20 hours postinjection. Time-dependent changes in percentage activity in source organs (kidneys, bladder, salivary glands, small intestine, liver, spleen, and whole body) were determined. Bone marrow and urinary bladder contents residence time were also calculated. Source organs residence time, organ-absorbed doses, and effective doses were determined using OLINDA/EXM software. RESULTS: Physiological tracer uptake was seen in kidneys, liver, spleen, small intestine, urinary bladder, and salivary glands and in metastases. Kidneys with highest radiation absorbed dose of 3.19E-01 mSv/MBq were the critical organs, followed by urinary bladder wall (2.24E-01 mSv/MBq, spleen [1.85E-01], salivary glands [1.11E-01], and liver [1.07E-01] mSv/MBq). Red marrow dose was found to be 3.31E-02 mSv/MBq. The mean effective dose of 3.89E-02 mSv/MBq and effective dose of 1.95 mSv was estimated from 50 MBq (treatment planning dose) of [Sc]Sc-PSMA-617. CONCLUSIONS: [Sc]Sc-PSMA-617 is found to be a very promising radiopharmaceutical that can be used for pre [Lu]Lu-PSMA-617 therapeutic dosimetric assessment.
