Fully-automated synthesis of 177Lu labelled FAPI derivatives on the module modular lab-Eazy

Eryilmaz, Kurtulus; Kılbaş, Benan

doi:10.1186/s41181-021-00130-3

Cited by 19 publications

(20 citation statements)

References 15 publications

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“…A combined [18F]FDG and FAPi PET imaging approach to determine the relationship between tumor and stroma can therefore be highly informative [201,202]. Moreover, FAPi can serve as a theranostic: the high TBR can be exploited by labeling FAPi with alpha-or beta-emitting isotopes to generate a potentially potent therapy [203][204][205].…”

Section: Cancer-associated Fibroblasts (Cafs)mentioning

confidence: 99%

NSCLC Biomarkers to Predict Response to Immunotherapy with Checkpoint Inhibitors (ICI): From the Cells to In Vivo Images

Liberini

Mariniello

Righi

et al. 2021

Cancers

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Lung cancer remains the leading cause of cancer-related death, and it is usually diagnosed in advanced stages (stage III or IV). Recently, the availability of targeted strategies and of immunotherapy with checkpoint inhibitors (ICI) has favorably changed patient prognosis. Treatment outcome is closely related to tumor biology and interaction with the tumor immune microenvironment (TME). While the response in molecular targeted therapies relies on the presence of specific genetic alterations in tumor cells, accurate ICI biomarkers of response are lacking, and clinical outcome likely depends on multiple factors that are both host and tumor-related. This paper is an overview of the ongoing research on predictive factors both from in vitro/ex vivo analysis (ranging from conventional pathology to molecular biology) and in vivo analysis, where molecular imaging is showing an exponential growth and use due to technological advancements and to the new bioinformatics approaches applied to image analyses that allow the recovery of specific features in specific tumor subclones.

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Section: Cancer-associated Fibroblasts (Cafs)mentioning

confidence: 99%

NSCLC Biomarkers to Predict Response to Immunotherapy with Checkpoint Inhibitors (ICI): From the Cells to In Vivo Images

Liberini

Mariniello

Righi

et al. 2021

Cancers

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show abstract

“…A combined [18F]FDG and FAPi PET imaging approach to determine the relationship between tumor and stroma can therefore be highly informative [191,192]. Moreover, FAPi can serve as theranostic: the high TBR can be exploited by labeling FAPi with alpha-or beta-emitting isotopes to generate a potentially potent therapy [193][194][195].…”

Section: Cancer-associated Fibroblasts (Cafs)mentioning

confidence: 99%

NSCLC Biomarkers to Predict Response to Immunotherapy with Checkpoint Inhibitors (ICI): From the Cells to in-Vivo Images

Liberini

Mariniello

Righi

et al. 2021

Preprint

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Lung cancer remains the leading cause of cancer-related death and it is usually diagnosed in advanced stages (stage III or IV). Recently, the availability of targeted strategies and of immunotherapy with checkpoint inhibitors (ICI) has favorably changed patient prognosis. Treatment outcome is closely related to tumor biology and interaction with the host immune microenvironment (TME). Whether for targeted therapies the response relies on the presence of specific genetic alterations in tumor cells, for ICI accurate biomarkers of response are lacking and clinical outcome likely depends on multiple factors, host and tumor-related. This paper is an overview of the ongoing research on predictive factors both from in-vitro/ex-vivo analysis (ranging from conventional pathology to molecular biology) and in-vivo analysis, where molecular imaging is showing an exponential growth and use due to the technological advancement and to the new bioinformatics approaches applied to image analyses that allow specific features recovery in specific tumor subclones.

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“…The aim of this work was to evaluate the efficiency and reliability of the radiosynthesis of 225 Ac-labeled DOTA-conjugated peptides and establish the translation of the synthesis to an automated synthesis platform (Modular-Lab EAZY, Eckert & Ziegler) for clinical routine production [24]. The ML EAZY is a cassette-based module operated with GMP-compliant software [25].…”

Section: Introductionmentioning

confidence: 99%

Ac-EAZY! Towards GMP-Compliant Module Syntheses of 225Ac-Labeled Peptides for Clinical Application

Pretze

Kunkel²,

Runge

et al. 2021

Pharmaceuticals

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The application of 225Ac (half-life T1/2 = 9.92 d) dramatically reduces the activity used for peptide receptor radionuclide therapy by a factor of 1000 in comparison to 90Y, 177Lu or 188Re while maintaining the therapeutic outcome. Additionally, the range of alpha particles of 225Ac and its daughter nuclides in tissue is much lower (47–85 μm for alpha energies Eα = 5.8–8.4 MeV), which results in a very precise dose deposition within the tumor. DOTA-conjugated commercially available peptides used for endoradiotherapy, which can readily be labeled with 177Lu or 90Y, can also accommodate 225Ac. The benefits are lower doses in normal tissue for the patient, dose reduction of the employees and environment and less shielding material. The low availability of 225Ac activity is preventing its application in clinical practice. Overcoming this barrier would open a broad field of 225Ac therapy. Independent which production pathway of 225Ac proves the most feasible, the use of automated synthesis and feasible and reproducible patient doses are needed. The Modular-Lab EAZY is one example of a GMP-compliant system, and the cassettes used for synthesis are small. Therefore, also the waste after the synthesis can be minimized. In this work, two different automated setups with different purification systems are presented. In its final configuration, three masterbatches were performed on the ML EAZY for DOTA-TATE and PSMA-I&T, respectively, fulfilling all quality criteria with final radiochemical yields of 80–90% for the 225Ac-labeled peptides.

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Fully-automated synthesis of 177Lu labelled FAPI derivatives on the module modular lab-Eazy

Cited by 19 publications

References 15 publications

NSCLC Biomarkers to Predict Response to Immunotherapy with Checkpoint Inhibitors (ICI): From the Cells to In Vivo Images

NSCLC Biomarkers to Predict Response to Immunotherapy with Checkpoint Inhibitors (ICI): From the Cells to In Vivo Images

NSCLC Biomarkers to Predict Response to Immunotherapy with Checkpoint Inhibitors (ICI): From the Cells to in-Vivo Images

Ac-EAZY! Towards GMP-Compliant Module Syntheses of 225Ac-Labeled Peptides for Clinical Application

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