A Systematic Review and Meta-analysis of the Effectiveness and Toxicities of Lutetium-177–labeled Prostate-specific Membrane Antigen–targeted Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer

Sadaghiani, Mohammad Salehi; Sheikhbahaei, Sara; Werner, Rudolf A.; Pienta, Kenneth J.; Pomper, Martin G.; Solnes, Lilja B.; Gorin, Michael A.; Wang, Nae Yuh; Rowe, Steven P.

doi:10.1016/j.eururo.2021.03.004

Cited by 70 publications

(77 citation statements)

References 58 publications

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“…Moreover, up to 30% of patients have never responded to this therapy, developed resistance, or suffered from serious hematological toxicity. The limitations of beta-emitter-based therapies may be linked to insufficient dose delivery to the tumor and the low linear-energy transfer of β-particles [4,5].…”

Section: Introductionmentioning

confidence: 99%

Design and Evaluation of 223Ra-Labeled and Anti-PSMA Targeted NaA Nanozeolites for Prostate Cancer Therapy—Part II. Toxicity, Pharmacokinetics and Biodistribution

Lankoff

Czerwińska

Walczak

et al. 2021

IJMS

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Metastatic castration-resistant prostate cancer (mCRPC) is a progressive and incurable disease with poor prognosis for patients. Despite introduction of novel therapies, the mortality rate remains high. An attractive alternative for extension of the life of mCRPC patients is PSMA-based targeted radioimmunotherapy. In this paper, we extended our in vitro study of 223Ra-labeled and PSMA-targeted NaA nanozeolites [223RaA-silane-PEG-D2B] by undertaking comprehensive preclinical in vitro and in vivo research. The toxicity of the new compound was evaluated in LNCaP C4-2, DU-145, RWPE-1 and HPrEC prostate cells and in BALB/c mice. The tissue distribution of 133Ba- and 223Ra-labeled conjugates was studied at different time points after injection in BALB/c and LNCaP C4-2 tumor-bearing BALB/c Nude mice. No obvious symptoms of antibody-free and antibody-functionalized nanocarriers cytotoxicity and immunotoxicity was found, while exposure to 223Ra-labeled conjugates resulted in bone marrow fibrosis, decreased the number of WBC and platelets and elevated serum concentrations of ALT and AST enzymes. Biodistribution studies revealed high accumulation of 223Ra-labeled conjugates in the liver, lungs, spleen and bone tissue. Nontargeted and PSMA-targeted radioconjugates exhibited a similar, marginal uptake in tumour lesions. In conclusion, despite the fact that NaA nanozeolites are safe carriers, the intravenous administration of NaA nanozeolite-based radioconjugates is dubious due to its high accumulation in the lungs, liver, spleen and bones.

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Section: Introductionmentioning

confidence: 99%

Design and Evaluation of 223Ra-Labeled and Anti-PSMA Targeted NaA Nanozeolites for Prostate Cancer Therapy—Part II. Toxicity, Pharmacokinetics and Biodistribution

Lankoff

Czerwińska

Walczak

et al. 2021

IJMS

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“…The alpha-emitter radium-223 demonstrated significantly prolonged overall survival and a favorable safety profile versus placebo in men with metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 ALSYMPCA trial (1). Lutetium-177-prostate-specific membrane antigen ligand ( 177 Lu-PSMA) is an investigational beta-emitting radioligand with accumulating evidence of clinical efficacy and acceptable toxicity in men with advanced-stage mCRPC (2)(3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

¹⁷⁷Lu-Prostate-Specific Membrane Antigen Ligand After ²²³Ra Treatment in Men with Bone-Metastatic Castration-Resistant Prostate Cancer: Real-World Clinical Experience

et al. 2021

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“…However, metastasis-targeting therapy might improve the outcome for patients with oligometastatic prostate cancer [ 1 , 2 ]. An increasing amount of clinical evidence suggests that radionuclide therapy using prostate-specific membrane antigen (PSMA) ligands could be developed into a powerful tool for the treatment of metastases of prostate cancer [ 3 , 4 ]. Still, up to 24% of patients with metastatic prostate cancer have too-low PSMA expression and are not eligible for PSMA-targeted treatment [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Influence of the Position and Composition of Radiometals and Radioiodine Labels on Imaging of Epcam Expression in Prostate Cancer Model Using the DARPin Ec1

Deyev

Liu

et al. 2021

Cancers

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The epithelial cell adhesion molecule (EpCAM) is intensively overexpressed in 40–60% of prostate cancer (PCa) cases and can be used as a target for the delivery of drugs and toxins. The designed ankyrin repeat protein (DARPin) Ec1 has a high affinity to EpCAM (68 pM) and a small size (18 kDa). Radiolabeled Ec1 might be used as a companion diagnostic for the selection of PCa patients for therapy. The study aimed to investigate the influence of radiolabel position (N- or C-terminal) and composition on the targeting and imaging properties of Ec1. Two variants, having an N- or C-terminal cysteine, were produced, site-specifically conjugated to a DOTA chelator and labeled with cobalt-57, gallium-68 or indium-111. Site-specific radioiodination was performed using ((4-hydroxyphenyl)-ethyl)maleimide (HPEM). Biodistribution of eight radiolabeled Ec1-probes was measured in nude mice bearing PCa DU145 xenografts. In all cases, positioning of a label at the C-terminus provided the best tumor-to-organ ratios. The non-residualizing [125I]I-HPEM label provided the highest tumor-to-muscle and tumor-to-bone ratios and is more suitable for EpCAM imaging in early-stage PCa. Among the radiometals, indium-111 provided the highest tumor-to-blood, tumor-to-lung and tumor-to-liver ratios and could be used at late-stage PCa. In conclusion, label position and composition are important for the DARPin Ec1.

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A Systematic Review and Meta-analysis of the Effectiveness and Toxicities of Lutetium-177–labeled Prostate-specific Membrane Antigen–targeted Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer

Cited by 70 publications

References 58 publications

Design and Evaluation of 223Ra-Labeled and Anti-PSMA Targeted NaA Nanozeolites for Prostate Cancer Therapy—Part II. Toxicity, Pharmacokinetics and Biodistribution

Design and Evaluation of 223Ra-Labeled and Anti-PSMA Targeted NaA Nanozeolites for Prostate Cancer Therapy—Part II. Toxicity, Pharmacokinetics and Biodistribution

¹⁷⁷Lu-Prostate-Specific Membrane Antigen Ligand After ²²³Ra Treatment in Men with Bone-Metastatic Castration-Resistant Prostate Cancer: Real-World Clinical Experience

Influence of the Position and Composition of Radiometals and Radioiodine Labels on Imaging of Epcam Expression in Prostate Cancer Model Using the DARPin Ec1

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A Systematic Review and Meta-analysis of the Effectiveness and Toxicities of Lutetium-177–labeled Prostate-specific Membrane Antigen–targeted Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer

Cited by 70 publications

References 58 publications

Design and Evaluation of 223Ra-Labeled and Anti-PSMA Targeted NaA Nanozeolites for Prostate Cancer Therapy—Part II. Toxicity, Pharmacokinetics and Biodistribution

Design and Evaluation of 223Ra-Labeled and Anti-PSMA Targeted NaA Nanozeolites for Prostate Cancer Therapy—Part II. Toxicity, Pharmacokinetics and Biodistribution

177Lu-Prostate-Specific Membrane Antigen Ligand After 223Ra Treatment in Men with Bone-Metastatic Castration-Resistant Prostate Cancer: Real-World Clinical Experience

Influence of the Position and Composition of Radiometals and Radioiodine Labels on Imaging of Epcam Expression in Prostate Cancer Model Using the DARPin Ec1

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¹⁷⁷Lu-Prostate-Specific Membrane Antigen Ligand After ²²³Ra Treatment in Men with Bone-Metastatic Castration-Resistant Prostate Cancer: Real-World Clinical Experience