Advances in 177Lu-PSMA and 225Ac-PSMA Radionuclide Therapy for Metastatic Castration-Resistant Prostate Cancer

Ling, Sui Wai; Blois, Erik de; Hooijman, Eline; Veldt, Astrid A.M. van der; Brabander, Tessa

doi:10.3390/pharmaceutics14102166

Cited by 36 publications

(23 citation statements)

References 73 publications

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“…At the moment of writing, formal phase I studies according full GMP with Ac-225 labelled radiopharmaceuticals are rare. Most of the studies are based on (small) retrospective studies (Ling, et al 2022 ; Morgenstern et al 2018 , 2020 ). In this chapter, some practical aspects of the clinical application related to the use of Ac-225 are summarized.…”

Section: Clinical Targeted Alpha Therapymentioning

confidence: 99%

“…Although the radionuclide therapy using beta-emitters is particularly suited to deliver high radiation dose to the tumor tissue, the therapeutic effect is in some cases limited even after several treatment cycles (Ling et al 2022 ). As described in the literature (Seo 2019 ; Kratochwil et al 2019 ; Ruigrok 2022 ; Scheinberg and McDevitt 2011 ; Graf et al 2014 ), alpha particle emission provides an advantage over beta-emission due to the high linear energy transfer (LET) and the short tissue penetration (50–100 µm) which results in localized dose effects and high local toxicity (Nelson et al 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…As described in the literature (Seo 2019 ; Kratochwil et al 2019 ; Ruigrok 2022 ; Scheinberg and McDevitt 2011 ; Graf et al 2014 ), alpha particle emission provides an advantage over beta-emission due to the high linear energy transfer (LET) and the short tissue penetration (50–100 µm) which results in localized dose effects and high local toxicity (Nelson et al 2020 ). Initial studies tentatively show that patients who have developed radio-resistance to for example [ 177 Lu]Lu-PSMA-617, can still benefit from treatment with targeted alpha therapy (TAT) using [ 225 Ac]Ac-PSMA-617 (Ling et al 2022 ; Feuerecker et al 2021 ; Okamoto et al 2021 ). Currently, different alpha-emitters are implemented in a clinical setting, such as [ 223 Ra]RaCl 2 (Xofigo®), [ 212 Pb]Pb-DOTAMTATE and [225Ac]Ac-PSMA/ [225Ac]Ac-DOTA-TATE (Kratochwil et al 2018 , 2019 ; Feuerecker et al 2021 ; Filippi et al 2020 ; Hooijman, et al 2021 ; Lunger et al 2021 ; Ma et al 2022 ; Morgenstern et al 2018 ; Shi et al 2022 ), in this manuscript, we focus on Ac-225 specifically.…”

Section: Introductionmentioning

confidence: 99%

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Implementing Ac-225 labelled radiopharmaceuticals: practical considerations and (pre-)clinical perspectives

Hooijman,

Radchenko,

Ling

et al. 2024

EJNMMI radiopharm. chem.

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Background In the past years, there has been a notable increase in interest regarding targeted alpha therapy using Ac-225, driven by the observed promising clinical anti-tumor effects. As the production and technology has advanced, the availability of Ac-225 is expected to increase in the near future, making the treatment available to patients worldwide. Main body Ac-225 can be labelled to different biological vectors, whereby the success of developing a radiopharmaceutical depends heavily on the labelling conditions, purity of the radionuclide source, chelator, and type of quenchers used to avoid radiolysis. Multiple (methodological) challenges need to be overcome when working with Ac-225; as alpha-emission detection is time consuming and highly geometry dependent, a gamma co-emission is used, but has to be in equilibrium with the mother-nuclide. Because of the high impact of alpha emitters in vivo it is highly recommended to cross-calibrate the Ac-225 measurements for used quality control (QC) techniques (radio-TLC, HPLC, HP-Ge detector, and gamma counter). More strict health physics regulations apply, as Ac-225 has a high toxicity, thereby limiting practical handling and quantities used for QC analysis. Conclusion This overview focuses specifically on the practical and methodological challenges when working with Ac-225 labelled radiopharmaceuticals, and underlines the required infrastructure and (detection) methods for the (pre-)clinical application.

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Section: Clinical Targeted Alpha Therapymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Implementing Ac-225 labelled radiopharmaceuticals: practical considerations and (pre-)clinical perspectives

Hooijman,

Radchenko,

Ling

et al. 2024

EJNMMI radiopharm. chem.

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“…Prostate cancer (PCa) is the second most frequent malignancy worldwide, after lung cancer [ 1 ]. Promising results have been reported in patients with Metastatic castrationresistant prostate cancer (mCRPC) treated with Prostate-specific membrane antigen (PSMA) Radio-ligand therapy (RLT) [ 2 , 3 ]. More specifically, the -emitting Lu-177-PSMA-617 has been evaluated extensively in the TheraP [ 4 ] and VISION trial [ 5 ], two randomized controlled trials demonstrating that treatments combining Lu-177-PSMA-617 with standard care significantly prolonged progression-free survival and overall survival for mCRPC patients compared to standard treatment.…”

Section: Introductionmentioning

confidence: 99%

Comparison of a 3D CZT and conventional SPECT/CT system for quantitative Lu-177 SPECT imaging

Nuttens,

Schramm,

D’Asseler

et al. 2024

EJNMMI Phys

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Purpose Next-generation SPECT/CT systems with CdZnTe (CZT) digital detectors in a ring-like setup are emerging to perform quantitative Lu-177 SPECT imaging in clinical routine. It is essential to assess how the shorter acquisition time might affect the image quality and uncertainty on the mean absorbed dose of the tumors and organs at risk compared to a conventional system. Methods A NEMA Image Quality phantom was scanned with a 3D CZT SPECT/CT system (Veriton, by Spectrum Dynamics) using 6 min per bed position and with a conventional SPECT/CT system (Symbia T16, by Siemens) using 16 min per bed position. The sphere-to-background ratio was 12:1 and the background activity concentration ranged from 0.52 to 0.06 MBq/mL. A clinical reconstruction protocol for dosimetry purposes was determined for both systems by maximizing the sphere-to-background ratio while keeping the coefficient of variation of the background as low as possible. The corresponding image resolution was determined by the matching filter method and used for a dose uncertainty assessment of both systems following an established uncertainty model.. Results The optimized iterative reconstruction protocol included scatter and attenuation correction for both systems and detector response modeling for the Siemens system. For the 3D CZT system, 6 iterations and 8 subsets were combined with a Gaussian post-filter of 3 mm Full Width Half Maximum (FWHM) for post-smoothing. For the conventional system, 16 iterations and 16 subsets were applied with a Gaussian post-smoothing filter of 1 mm FWHM. For these protocols, the sphere-to-background ratio was 18.5% closer to the true ratio for the conventional system compared to the 3D CZT system when considering the four largest spheres. Meanwhile, the background coefficient of variation was very similar for both systems. These protocols resulted in SPECT image resolution of 14.8 mm and 13.6 mm for the 3D CZT and conventional system respectively. Based on these resolution estimates, a 50% dose uncertainty corresponded to a lesion volume of 28 mL for the conventional system and a lesion volume of 33 mL for the 3D CZT system. Conclusions An optimized reconstruction protocol for a Veriton system with 6 min of acquisition time per bed position resulted in slightly higher dose uncertainties than a conventional Symbia system using 16 min of acquisition time per bed position. Therefore, a 3D CZT SPECT/CT allows to significantly reduce the acquisition times with only a very limited impact on dose uncertainties such that quantitative Lu-177 SPECT/CT imaging becomes much more accessible for treatment concurrent dosimetry. Nevertheless, the uncertainty of SPECT-based dose estimates remains high.

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“…In the case of α-emitters, 213 Bi, 223 Ra, 211 At, and 225 Ac have been investigated for the treatment of cancer metastases due to their apoptotic effects [ 39 ]. Various theragnostic strategies involving them have been studied, and some radioisotopes, such as 225 Ac, have been utilised for cancer therapy in preclinical and clinical trials [ 40 , 41 , 42 , 43 ].…”

Section: Introductionmentioning

confidence: 99%

Advances in Radionuclides and Radiolabelled Peptides for Cancer Therapeutics

Chakraborty

Mondal

et al. 2023

Pharmaceutics

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Radiopharmaceutical therapy, which can detect and treat tumours simultaneously, was introduced more than 80 years ago, and it has changed medical strategies with respect to cancer. Many radioactive radionuclides have been developed, and functional, molecularly modified radiolabelled peptides have been used to produce biomolecules and therapeutics that are vastly utilised in the field of radio medicine. Since the 1990s, they have smoothly transitioned into clinical application, and as of today, a wide variety of radiolabelled radionuclide derivatives have been examined and evaluated in various studies. Advanced technologies, such as conjugation of functional peptides or incorporation of radionuclides into chelating ligands, have been developed for advanced radiopharmaceutical cancer therapy. New radiolabelled conjugates for targeted radiotherapy have been designed to deliver radiation directly to cancer cells with improved specificity and minimal damage to the surrounding normal tissue. The development of new theragnostic radionuclides, which can be used for both imaging and therapy purposes, allows for more precise targeting and monitoring of the treatment response. The increased use of peptide receptor radionuclide therapy (PRRT) is also important in the targeting of specific receptors which are overexpressed in cancer cells. In this review, we provide insights into the development of radionuclides and functional radiolabelled peptides, give a brief background, and describe their transition into clinical application.

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Advances in 177Lu-PSMA and 225Ac-PSMA Radionuclide Therapy for Metastatic Castration-Resistant Prostate Cancer

Cited by 36 publications

References 73 publications

Implementing Ac-225 labelled radiopharmaceuticals: practical considerations and (pre-)clinical perspectives

Implementing Ac-225 labelled radiopharmaceuticals: practical considerations and (pre-)clinical perspectives

Comparison of a 3D CZT and conventional SPECT/CT system for quantitative Lu-177 SPECT imaging

Advances in Radionuclides and Radiolabelled Peptides for Cancer Therapeutics

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