177Lu-FAPI Therapy in a Patient With End-Stage Metastatic Pancreatic Adenocarcinoma

Kaghazchi, Fatemeh; Aghdam, Ramin Akbarian; Haghighi, Shirin; Vali, Reza; Adinehpour, Zohreh

doi:10.1097/rlu.0000000000004021

Cited by 24 publications

(27 citation statements)

References 9 publications

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“…(9,(20)(21)(22)(23) While Lutathera® and PSMA-617 are characterized by a sustained tumour residence time in patients (i.e., ~61 hours for 177 Lu-PSMA-617 and ~88 hours for 177 Lu-DOTATATE) (24,25), SMRCs based on FAP-targeting agents are typically cleared from solid lesions in few hours. (26,27) In preclinical biodistribution experiments, 177 Lu-OncoFAP selectively localized on neoplastic lesions (~38% ID/g, 1h after systemic administration), but half of the dose delivered to the tumour was lost within 8-12 hours. (18) A comparable tumour targeting performance and pharmacokinetic profile have been reported for other FAP-targeting SMRCs by Haberkorn and co-workers (e.g., the tumour uptake of [ 177 Lu]Lu-FAPI-46 decreased from 12.5% ID/g at 1h to 2.5% ID/g at 24h after administration).…”

Section: Introductionmentioning

confidence: 99%

A Dimeric FAP-Targeting Small-Molecule Radioconjugate with High and Prolonged Tumor Uptake

et al. 2022

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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 [ 177 Lu]Lu-OncoFAP-DOTAGA ( 177 Lu-OncoFAP) and [ 177 Lu]Lu-BiOncoFAP-DOTAGA ( 177 Lu-BiOncoFAP) were performed in mice bearing FAP-positive HT-1080 tumours.Results: 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, 177 Lu-BiOncoFAP exhibited a more stable and prolonged tumour uptake than 177 Lu-OncoFAP (~20% ID/g vs ~4% ID/g, at 24h p.i., respectively). Notably, 177 Lu-BiOncoFAP showed favorable tumour-to-organ ratios with low kidney uptake. Both 177 Lu-OncoFAP and 177 Lu-BiOncoFAP displayed potent anti-tumour efficacy when administered at therapeutic doses in tumour bearing mice. Conclusions:177 Lu-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 Dimeric FAP-Targeting Small-Molecule Radioconjugate with High and Prolonged Tumor Uptake

et al. 2022

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“…( 28 ) Importantly, a rapid washout from tumours is observed not only in mice but also in patients treated with [ 177 Lu]Lu-FAPI-46. ( 29 )…”

Section: Introductionmentioning

confidence: 99%

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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“…2,3 In the past 2 years, FAP-targeted radionuclide therapy with 177 Lu/ 90 Y-labeled FAPIs has been reported as a novel therapeutic option for some refractory cancers, including gastric, colorectal, pancreatic, and breast cancer. [4][5][6][7][8] In this case, we presented the experience of FAP-targeted radionuclide in a patient with advanced RAIR-DTC, the results demonstrated that multiple cycles of 177 Lu-FAPI-46 treatment was well tolerated by the patient, providing a novel treatment strategy for patients with advanced RAIR-DTC. Further research on improving the pharmacokinetic properties of FAPI tracers may be necessary.…”

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confidence: 99%

FAP-Targeted Radionuclide Therapy of Advanced Radioiodine-Refractory Differentiated Thyroid Cancer With Multiple Cycles of 177Lu-FAPI-46

Huang

Sun

et al. 2022

Clin Nucl Med

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Many recent studies began to explore the therapeutic potential of FAP-targeted radionuclide therapy for refractory cancers. In this case, we presented the experience of multiple cycles of 177Lu-FAPI-46 radionuclide therapy in a 34-year-old man with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). Intense radiotracer uptake was observed in RAIR-DTC metastatic lesions on the pretreatment 68Ga-FAPI PET/CT and posttherapeutic scintigraphy. Follow-up examinations after 4 cycles of 177Lu-FAPI-46 treatment revealed stable metastatic lesions, resulting in stable disease. This case demonstrated the potential feasibility of 177Lu-FAPI-46 in the treatment of advanced RAIR-DTC; further research on improving the FAP-targeting vector may be necessary.

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177Lu-FAPI Therapy in a Patient With End-Stage Metastatic Pancreatic Adenocarcinoma

Cited by 24 publications

References 9 publications

A Dimeric FAP-Targeting Small-Molecule Radioconjugate with High and Prolonged Tumor Uptake

A Dimeric FAP-Targeting Small-Molecule Radioconjugate with High and Prolonged Tumor Uptake

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

FAP-Targeted Radionuclide Therapy of Advanced Radioiodine-Refractory Differentiated Thyroid Cancer With Multiple Cycles of 177Lu-FAPI-46

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