Preparation of 177Lu-PSMA-617 in Hospital Radiopharmacy: Convenient Formulation of a Clinical Dose Using a Single-Vial Freeze-Dried PSMA-617 Kit Developed In-House.

Abstract

OBJECTIVE:

In the recent time, endoradionuclide therapy for metastatic castration-resistant prostate carcinoma employing 177Lu-PSMA-617 has yielded encouraging results and several clinical trials with the agent are currently ongoing. Routine preparation of 177Lu-PSMA-617 patient doses can be made simpler and convenient, if the ingredients essential for radiolabeling are made available in a ready-to-use lyophilized form.

METHODS:

PSMA-617 freeze-dried kit was formulated and used for the preparation of 177Lu-PSMA-617 clinical dose with high radiochemical purity using low/medium specific activity 177Lu. Detailed radiochemical studies were performed to determine the maximum activity and volume of 177LuCl3, which can be added in the kit for the formulation of 177Lu-PSMA-617. Studies were also performed to determine the shelf life of the kit to ensure its long-term usage. Studies were performed in buffer as well as human serum medium to determine the stability of the 177Lu-PSMA-617 complex after storing in respective media up to 7 days postpreparation. About ten patient doses of 177Lu-PSMA-617 were administered, and posttherapy scans were acquired.

RESULTS:

The formulated freeze-dried kit of PSMA-617 could be radiolabeled with an average percentage radiochemical purity > 98.53 ± 0.38. The freeze-dried kit was found suitable for tolerating up to 0.5 mL of 177LuCl3 (in 0.01 N HCl) and specific activity of 555 MBq/μg (15 mCi/μg) for the preparation of the patient dose of 177Lu-PSMA-617. The 177Lu-PSMA-617 complex prepared using the freeze-dried kit of PSMA-617 was observed to maintain % radiochemical purity (RCP) of 96.74 ± 0.87 and 94.81 ± 2.66, respectively, even after storing up to 7 days in buffer and human serum, respectively. 177Lu-PSMA-617 prepared using the in-house formulated freeze-dried kit of PSMA-617 exhibited accumulation in metastatic lesions picked up in a pretherapy PET scan. Reduction in number as well as size of lesions was observed in posttherapy scans acquired after two months of administering the first therapeutic dose of 177Lu-PSMA-617.

CONCLUSIONS:

The freeze-dried kit of PSMA-617 could be used for the preparation of 177Lu-PSMA-617 with high radiochemical purity (>98%) in a reproducible manner. 177Lu-PSMA-617 prepared using the developed kit was successfully evaluated in patients suffering from metastatic prostate cancer.

• Authors: Mohini Guleria, Jeyachitra Amirdhanayagam, Haladhar D Sarma, Ramya Priya Rallapeta, V S Krishnamohan, Ajit Nimmagadda, Parthasarathy Ravi, Sailaja Patri, Tekchand Kalawat, Tapas Das
• Journal: BioMed research international (Biomed Res Int) Vol. 2021 Pg. 1555712 ( 2021) ISSN: 2314-6141 [Electronic] United States
• PMID: 34845436 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Mohini Guleria et al.

Chemical References

• Dipeptides
• Heterocyclic Compounds, 1-Ring
• PSMA-617
• Radioisotopes
• Radiopharmaceuticals
• Lutetium
• Lutetium-177
• Prostate-Specific Antigen

Topics

• Animals
• Dipeptides (isolation & purification, pharmacokinetics, therapeutic use)
• Drug Compounding (methods)
• Drug Stability
• Freeze Drying
• Heterocyclic Compounds, 1-Ring (isolation & purification, pharmacokinetics, therapeutic use)
• Humans
• In Vitro Techniques
• Lutetium (isolation & purification, pharmacokinetics, therapeutic use)
• Male
• Nuclear Pharmacy (methods)
• Pharmacy Service, Hospital
• Positron Emission Tomography Computed Tomography
• Prostate-Specific Antigen (isolation & purification, pharmacokinetics, therapeutic use)
• Prostatic Neoplasms (diagnostic imaging, pathology, radiotherapy)
• Prostatic Neoplasms, Castration-Resistant (diagnostic imaging, pathology, radiotherapy)
• Radiochemistry (methods, standards)
• Radioisotopes (isolation & purification, pharmacokinetics, therapeutic use)
• Radiopharmaceuticals (isolation & purification, pharmacokinetics, therapeutic use)
• Rats
• Rats, Wistar
• Tissue Distribution