Recent Advances in Radiometals for Combined Imaging and Therapy in Cancer

Álvarez, Natalia; Bauer, David; Hernández-Gil, Javier; Lewis, Jason S.

doi:10.1002/cmdc.202100135

Cited by 67 publications

(56 citation statements)

References 332 publications

(365 reference statements)

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“…( 4 – 7 ) Patients who can predictably benefit from targeted radioligand therapy are accurately selected through dosimetry studies. ( 8 ) Lutathera®, a radioligand therapeutic targeting Somatostatin Receptor type 2 (SSTR-2), is the first SMRC product that gained marketing authorization for the therapy of neuroendocrine tumours (NETs). ( 9 ) The use of this drug has consistently shown high response rates and long median progression-free survival in a multicenter phase-III clinical trial.…”

Section: Introductionmentioning

confidence: 99%

A novel dimeric FAP-targeting small molecule-radio conjugate with high and prolonged tumour uptake

Galbiati

Zana

Bocci

et al. 2022

Preprint

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Imaging procedures based on small molecule-radio conjugates (SMRCs) targeting fibroblast activation protein (FAP) have recently emerged as a powerful tool for the diagnosis of a wide variety of tumours. However, the therapeutic potential of radiolabeled FAP-targeting agents is limited by their short residence time in neoplastic lesions. In this work, we present the development and in vivo characterization of BiOncoFAP, a new dimeric FAP-binding motif with extended tumour residence time and favorable tumour-to-organ ratio. Methods: The binding properties of BiOncoFAP and its monovalent OncoFAP analogue were assayed against recombinant hFAP. Preclinical experiments with [177Lu]Lu-OncoFAP-DOTAGA (177Lu-OncoFAP) and [177Lu]Lu-BiOncoFAP-DOTAGA (177Lu-BiOncoFAP) were performed in mice bearing FAP-positive HT-1080 tumours. OncoFAP and BiOncoFAP displayed comparable sub-nanomolar dissociation constants towards hFAP in solution, but the bivalent BiOncoFAP bound more avidly to the target immobilized on solid supports. In a comparative biodistribution study, 177Lu-BiOncoFAP exhibited a more stable and prolonged tumour uptake than 177Lu-OncoFAP (~20% ID/g vs ~4% ID/g, at 24h p.i., respectively). Notably, 177Lu-BiOncoFAP showed favorable tumour-to-organ ratios with low kidney uptake. Both 177Lu-OncoFAP and 177Lu-BiOncoFAP displayed potent anti-tumour efficacy when administered at therapeutic doses in tumour bearing mice. 177Lu-BiOncoFAP is a promising candidate for radioligand therapy of cancer, with favorable in vivo tumour-to-organ ratio, long tumour residence time and potent anti-cancer efficacy.

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Section: Introductionmentioning

confidence: 99%

A novel dimeric FAP-targeting small molecule-radio conjugate with high and prolonged tumour uptake

Galbiati

Zana

Bocci

et al. 2022

Preprint

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“…Of the two key components of these dual-modal agents, the fluorophore and radionuclide, the latter has been reviewed extensively, including in this volume [ 82 , 83 , 84 ]. Consequently, here we focus on the fluorophore component.…”

Section: Recent Developments In Nir and Swir Fluorophoresmentioning

confidence: 99%

Targeted Dual-Modal PET/SPECT-NIR Imaging: From Building Blocks and Construction Strategies to Applications

Usama

Marker

Vargas

et al. 2022

Cancers

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Molecular imaging is an emerging non-invasive method to qualitatively and quantitively visualize and characterize biological processes. Among the imaging modalities, PET/SPECT and near-infrared (NIR) imaging provide synergistic properties that result in deep tissue penetration and up to cell-level resolution. Dual-modal PET/SPECT-NIR agents are commonly combined with a targeting ligand (e.g., antibody or small molecule) to engage biomolecules overexpressed in cancer, thereby enabling selective multimodal visualization of primary and metastatic tumors. The use of such agents for (i) preoperative patient selection and surgical planning and (ii) intraoperative FGS could improve surgical workflow and patient outcomes. However, the development of targeted dual-modal agents is a chemical challenge and a topic of ongoing research. In this review, we define key design considerations of targeted dual-modal imaging from a topological perspective, list targeted dual-modal probes disclosed in the last decade, review recent progress in the field of NIR fluorescent probe development, and highlight future directions in this rapidly developing field.

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“…However, such strategies remain of interest for RIT or nuclear imaging applications, but these strategies still require optimization. Recent advances in phage-display technology, chemical and chemoenzymatic engineering, and radiolabeling protocols have introduced new insights to circumvent most of these drawbacks and have shown promising outcomes for antibody fragments in preclinical studies [ 5 , 119 ].…”

Section: Alternatives To Conventional Rit and Prospectsmentioning

confidence: 99%

“…An increasing panel of radionuclides with different properties (half-life, spectra emission, particles or electrons) is currently under evaluation in theranostic approaches (for a review see [ 5 ]). However, until now, the choice of radionuclides for RIT in clinical trials was limited to I-131 (8.0 days half-life), Y-90 (2.7 days half-life), Lu-177 (6.7 days half-life), and Re-188 (16.9 hours half-life) for β - -emitters and to Bi-213 (45.6 minutes half-life) and At-211 for α-particles (7.2 hours half-life).…”

Section: Introductionmentioning

confidence: 99%

Radioimmunotherapy in Oncology: Overview of the Last Decade Clinical Trials

Rondon

Rouanet

Degoul

2021

Cancers

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The specific irradiation of tumors with selective radiolabeled antibodies constitutes an attractive therapeutic approach. Consequent preclinical research has been conducted by both biologists to identify pertinent targets and to select corresponding antibodies (mAb) and by radiochemists to radiolabel mAbs. These numerous preclinical investigations have ascertained the therapeutic interest of radioimmunotherapy (RIT) protocols in mice models. Here, we summarize the clinical studies that have been performed the last decade, including clinical trials (phases I, II, and III), prospective and retrospective studies, and cases series. We thereby reported 92 clinical studies. Among them, 62 concern the treatment of hematological malignancies, and 30 concern solid tumors. For hematologic diseases, the analysis was complex due to the high discrepancy of therapeutic strategies (first-line therapy, consolidation, stem cell transplantation conditioning) as well as the high variety of malignancies that were treated. The clinical studies from the last decade failed to expand anti-CD20 RIT indications but confirmed that RIT using radiolabeled anti-CD20 remains a pertinent choice for patients with relapse follicular lymphomas. For solid tumors, the positive benefit of RIT is more mitigated, apart for few malignancies that can be treated locally. Clinical trials also demonstrated the potential of some antibody formats, such as F(ab′)2, which has already been approved by the China State FDA under the trend name Licartin®. Despite disparate results, mAb fragments are an interesting prospect for the improvement of RIT efficiency as well as for pretargeted strategies that delay the injection of radioactive treatments from the mAb ones.

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Recent Advances in Radiometals for Combined Imaging and Therapy in Cancer

Cited by 67 publications

References 332 publications

A novel dimeric FAP-targeting small molecule-radio conjugate with high and prolonged tumour uptake

A novel dimeric FAP-targeting small molecule-radio conjugate with high and prolonged tumour uptake

Targeted Dual-Modal PET/SPECT-NIR Imaging: From Building Blocks and Construction Strategies to Applications

Radioimmunotherapy in Oncology: Overview of the Last Decade Clinical Trials

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