Therapeutic Multidose Preparation of a Ready-to-Use <sup>177</sup>Lu-PSMA-617 Using Carrier Added Lutetium-177 in a Hospital Radiopharmacy and Its Clinical Efficacy

Ak, Chakraborty; Mitra, Arpit; Tawate, Megha; Sahoo, Sudip; Lad, Sangita; Rakshit, Sutapa; Gaikwad, Sujay; Basu, Sandip; Shimpi, Hemant; Banerjee, Sharmila

doi:10.1089/cbr.2020.4261

Cited by 3 publications

(4 citation statements)

References 16 publications

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“…The established RPC-and SEC-ICP-MS methods allowed the investigation of the in vitro chemical stability of 175 Lu-and nat Ga-labeled biomolecules. The stabilities measured for the non-radioactive [ 175 Lu]Lu-PSMA-617 and [ nat Ga]Ga-PSMA-11 were equal to the stabilities reported in the literature for the radioactive [ 177 Lu]Lu-PSMA-617 and [ 68 Ga]Ga-PSMA-11 [36,37], demonstrating the reliability of the developed method. Analysis of in vitro serum stability assays by SEC-ICP-MS required only a dilution of the sample after incubation in mouse serum.…”

Section: Discussionsupporting

confidence: 65%

Liquid Chromatography ICP-MS to Assess the Stability of 175Lu- and natGa-Based Tumor-Targeting Agents towards the Development of 177Lu- and 68Ga-Labeled Radiopharmaceuticals

Wallimann,

Hensinger,

Müller

et al. 2024

Pharmaceutics

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In recent years, nuclear medicine has gained great interest, partly due to the success story of [177Lu]Lu-PSMA-617 (PluvictoTM). Still, in-depth preclinical characterization of radiopharmaceuticals mainly happens at centers that allow working with radioactive material. To support the development of novel radiopharmaceuticals, alternative non-radioactive characterization assays are highly desirable. The aim of this study was to demonstrate that inductively coupled plasma mass spectrometry (ICP-MS) associated with a chromatographic system can serve as a surrogate for the classical high-performance liquid chromatography (HPLC)-radiodetector combination for preclinical in vitro characterization of non-radioactive metal-labeled analogs of radiopharmaceuticals. In this proof-of-concept study, we demonstrate the applicability of HPLC–ICP-MS by assessing the stability of 175Lu- and natGa-labeled prostate-specific membrane antigen (PSMA)-targeting peptidomimetics, single domain antibody (sdAb) conjugates, and monoclonal antibody (mAb) conjugates. 175Lu-labeled DOTAGA-conjugated and natGa-labeled NODAGA-conjugated sdAbs and mAbs showed the highest stability with >90% still intact after 24 h. The peptidomime-tics [175Lu]Lu-PSMA-617 and [natGa]Ga-PSMA-11 showed identical in vitro serum stability as it was reported for their corresponding radioligands with >99% intact species after 24 h incubation in mouse serum, demonstrating the reliability of the method. Hence, the established HPLC–ICP-MS methods can support the development of novel radiopharmaceuticals in a classical pharmaceutical setting.

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Section: Discussionsupporting

confidence: 65%

Liquid Chromatography ICP-MS to Assess the Stability of 175Lu- and natGa-Based Tumor-Targeting Agents towards the Development of 177Lu- and 68Ga-Labeled Radiopharmaceuticals

Wallimann,

Hensinger,

Müller

et al. 2024

Pharmaceutics

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“…A comparison of the present work with the similar studies reported in the contemporary literature revealed few important features of the present study ( Table 4 ). Though the formulation of 177 Lu-PSMA-617 has been reported widely [ 21 , 34 – 37 ], comparison of the present work was primarily made only with those studies where emphasis was given on the radiochemical parameters for the formulation of patient doses of 177 Lu-PSMA-617 [ 35 – 37 ]. While the majority of these studies described ready-to-use multidose formulation of 177 Lu-PSMA-617 [ 35 , 36 ], the present work describes formulation of a single patient dose of the agent using a freeze-dried kit.…”

Section: Discussionmentioning

confidence: 99%

“…Though the formulation of 177 Lu-PSMA-617 has been reported widely [ 21 , 34 – 37 ], comparison of the present work was primarily made only with those studies where emphasis was given on the radiochemical parameters for the formulation of patient doses of 177 Lu-PSMA-617 [ 35 – 37 ]. While the majority of these studies described ready-to-use multidose formulation of 177 Lu-PSMA-617 [ 35 , 36 ], the present work describes formulation of a single patient dose of the agent using a freeze-dried kit. Therefore, a direct comparison of the present work with these studies cannot be made.…”

Section: Discussionmentioning

confidence: 99%

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

Guleria

Amirdhanayagam

Sarma

et al. 2021

BioMed Research International

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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.

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“…The production and quality control recommendations of the joint International Atomic Energy Agency, European Association of Nuclear Medicine, and Society of Nuclear Medicine and Molecular Imaging on peptide receptor radionuclide therapy for neuroendocrine tumors are applicable to 177 Lu-PSMA RLT (26). 177 Lu-PSMA consists of a pharmacophore (PSMA) conjugated with a chelating moiety (DOTA) to bind to the 177 Lu radiometal (27). The DOTA-PSMA precursor is typically produced under goodmanufacturing-practice conditions by a commercial supplier such as ABX.…”

Section: Technical Considerationsmentioning

confidence: 99%

¹⁷⁷Lu-PSMA Therapy

Parent

Savir-Baruch²,

Gayed³

et al. 2022

J. Nucl. Med. Technol.

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CE credit: For CE credit, you can access the test for this article, as well as additional JNMT CE tests, online at https://www.snmmilearningcenter.org. Complete the test online no later than September 2025. Your online test will be scored immediately. You may make 3 attempts to pass the test and must answer 75% of the questions correctly to receive Continuing Education Hour (CEH) credit. Credit amounts can be found in the SNMMI Learning Center Activity. SNMMI members will have their CEH credit added to their VOICE transcript automatically; nonmembers will be able to print out a CE certificate upon successfully completing the test. The online test is free to SNMMI members; nonmembers must pay $15.00 by credit card when logging onto the website to take the test.Radiopharmaceutical therapy using 177 Lu-prostate-specific membrane antigen (PSMA) is an effective prostate cancer treatment that was recently approved by the U.S. Food and Drug Administration. This method leverages the success of PSMAtargeted PET imaging, enabling delivery of targeted radiopharmaceutical therapy; has demonstrated a clear benefit in large prospective clinical trials; and promises to become part of the standard armamentarium of treatment for patients with prostate cancer. This review highlights the evidence supporting the use of this agent, along with important areas under investigation. Practical information on technology aspects, dose administration, nursing, and the role of the treating physician is highlighted. Overall, 177 Lu-PSMA treatment requires close collaboration among referring physicians, nuclear medicine technologists, radiopharmacists, and nurses to streamline patient care.

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Therapeutic Multidose Preparation of a Ready-to-Use ¹⁷⁷Lu-PSMA-617 Using Carrier Added Lutetium-177 in a Hospital Radiopharmacy and Its Clinical Efficacy

Cited by 3 publications

References 16 publications

Liquid Chromatography ICP-MS to Assess the Stability of 175Lu- and natGa-Based Tumor-Targeting Agents towards the Development of 177Lu- and 68Ga-Labeled Radiopharmaceuticals

Liquid Chromatography ICP-MS to Assess the Stability of 175Lu- and natGa-Based Tumor-Targeting Agents towards the Development of 177Lu- and 68Ga-Labeled Radiopharmaceuticals

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

¹⁷⁷Lu-PSMA Therapy

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Therapeutic Multidose Preparation of a Ready-to-Use 177Lu-PSMA-617 Using Carrier Added Lutetium-177 in a Hospital Radiopharmacy and Its Clinical Efficacy

Cited by 3 publications

References 16 publications

Liquid Chromatography ICP-MS to Assess the Stability of 175Lu- and natGa-Based Tumor-Targeting Agents towards the Development of 177Lu- and 68Ga-Labeled Radiopharmaceuticals

Liquid Chromatography ICP-MS to Assess the Stability of 175Lu- and natGa-Based Tumor-Targeting Agents towards the Development of 177Lu- and 68Ga-Labeled Radiopharmaceuticals

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

177Lu-PSMA Therapy

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Therapeutic Multidose Preparation of a Ready-to-Use ¹⁷⁷Lu-PSMA-617 Using Carrier Added Lutetium-177 in a Hospital Radiopharmacy and Its Clinical Efficacy

¹⁷⁷Lu-PSMA Therapy