90Y/177Lu-DOTATOC: From Preclinical Studies to Application in Humans

Uccelli, Licia; Boschi, Alessandra; Cittanti, Corrado; Martini, Petra; Panareo, Stefano; Tonini, Eugenia; Nieri, Alberto; Urso, Luca; Caracciolo, Matteo; Lodi, Leda; Carnevale, Aldo; Giganti, Melchiore; Bartolomei, Mirco

doi:10.3390/pharmaceutics13091463

Cited by 23 publications

(12 citation statements)

References 93 publications

(181 reference statements)

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“…In mRCC patients with high PSMA avidity, another future perspective is represented by Radioligand Therapy. In a theranostic approach, mRCC could be first imaged with PSMA PET/CT and subsequently treated with PSMA labeled with β-emitting (such as 177 Lu or 90 Y) or α-emitting (such as 225 Ac) radionuclides, as it happens today for neuroendocrine tumors and prostate cancer (Zhang et al 2021 ; Uccelli et al 2021 ). This approach could be particularly useful in chrRCC, where PSMA expression is usually high and therapeutic options are limited (Baccala et al 2007 ; Spatz et al 2018 ; Toyama et al 2021 ).…”

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

Role of PSMA-ligands imaging in Renal Cell Carcinoma management: current status and future perspectives

Urso

Castello

Rocca

et al. 2022

J Cancer Res Clin Oncol

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Background Renal masses detection is continually increasing worldwide, with Renal Cell Carcinoma (RCC) accounting for approximately 90% of all renal cancers and remaining one of the most aggressive urological malignancies. Despite improvements in cancer management, accurate diagnosis and treatment strategy of RCC by computed tomography (CT) and magnetic resonance imaging (MRI) are still challenging. Prostate-Specific Membrane Antigen (PSMA) is known to be highly expressed on the endothelial cells of the neovasculature of several solid tumors other than prostate cancer, including RCC. In this context, recent preliminary studies reported a promising role for positron emission tomography (PET)/CT with radiolabeled molecules targeting PSMA, in alternative to fluorodeoxyglucose (FDG) in RCC patients. Purpose The aim of our review is to provide an updated overview of current evidences and major limitations regarding the use of PSMA PET/CT in RCC. Methods A literature search, up to 31 December 2021, was performed using the following electronic databases: PubMed, SCOPUS, Web of Science, and Google Scholar. Results The findings of this review suggest that PSMA PET/CT could represent a valid imaging option for diagnosis, staging, and therapy response evaluation in RCC, particularly in clear cell RCC. Conclusions Further studies are needed for this “relatively” new imaging modality to consolidate its indications, timing, and practical procedures.

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Section: Discussion and Future Perspectivesmentioning

confidence: 99%

Role of PSMA-ligands imaging in Renal Cell Carcinoma management: current status and future perspectives

Urso

Castello

Rocca

et al. 2022

J Cancer Res Clin Oncol

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“…In recent years, we have been witnessing an impressive development in the field of targeted radionuclide therapy, firstly with the approval of 223 Ra-therapy for PCa therapy, then followed by the authorization of [ 177 Lu]Lu-oxodotreotide for the management of neuroendocrine tumors (NET) and, even more recently, by the implementation of [ 177 Lu]Lu-PSMA-617 for mCRPC [ 14 , 29 , 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

DNA Damage Repair Defects and Targeted Radionuclide Therapies for Prostate Cancer: Does Mutation Really Matter? A Systematic Review

Filippi

Palumbo²,

Bagni³

et al. 2022

Life

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The aim of the present review was to assess the impact of DNA damage repair (DDR) mutations on response and outcome of patients (pts) affected by advanced prostate cancer (PCa) submitted to radionuclide therapies with [223Ra]RaCl2 (223Ra-therapy) or prostate specific membrane antigen (PSMA) ligands. A systematic literature search according to PRISMA criteria was made by using two main databases. Only studies published up until to October 2022 in the English language with ≥10 enrolled patients were selected. Seven studies including 326 pts, of whom 201 (61.6%) harboring DDR defects, were selected. The majority of selected papers were retrospective and four out of seven (57.1%) had small sample size (<50 pts). Three out of seven (42.8%) studies reported a more favorable outcome (overall or progression free survival) after therapy with alpha emitters (223Ra-therapy or [225Ac]Ac-PSMA-617) in subjects with DDR defects with respect to those without mutations. In two studies employing alpha or beta emitters ([177Lu]/[225Ac]-PMSA), no significant benefit was registered in pts harboring DDR defects. In all but one paper, no significant difference in response rate was reported among pts with or without DDR mutations. Although preliminary and biased by the retrospective design, preliminary data suggest a trend towards a longer survival in PCa pts harboring DDR defects submitted to radionuclide targeted therapy with alpha emitters.

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“…According to a theranostic approach, SSTa can bind a positron-emitting isotope, [ 68 Ga]Ga, for diagnostic purposes ([ 68 Ga]Ga-DOTA-SSTa PET/CT) or a high-energy beta emitter, such as [ 90 Y]Y or [ 177 Lu]Lu, for radioligand therapy (RLT) [ 6 ]. In particular, [ 68 Ga]Ga-DOTA-SSTa PET/CT contributes to the initial characterization of the neuroendocrine lesions, to the staging and re-staging of the NEN patients over time and, above all, to the selection of those patients who will be candidates for RLT [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Glucose Metabolism Modification Induced by Radioligand Therapy with [177Lu]Lu/[90Y]Y-DOTATOC in Advanced Neuroendocrine Neoplasms: A Prospective Pilot Study within FENET-2016 Trial

Urso

Panareo²,

Castello

et al. 2022

Pharmaceutics

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[18F]F-FDG (FDG) PET is emerging as a relevant diagnostic and prognostic tool in neuroendocrine neoplasms (NENs), as a simultaneous decrease in [68Ga]Ga-DOTA peptides and increase in FDG uptake (the “flip-flop” phenomenon) occurs during the natural history of these tumors. The aim of this study was to evaluate the variations on FDG PET in NEN patients treated with two different schemes of radioligand therapy (RLT) and to correlate them with clinical–pathologic variables. A prospective evaluation of 108 lesions in 56 patients (33 males and 23 females; median age, 64.5 years) affected by NENs of various primary origins (28 pancreatic, 13 gastrointestinal, 9 bronchial, 6 unknown primary (CUP-NENs) and 1 pheochromocytoma) and grades (median Ki-67 = 9%) was performed. The patients were treated with RLT within the phase II clinical trial FENET-2016 (CTID: NCT04790708). RLT was offered for 32 patients with the MONO scheme (five cycles of [177Lu]Lu-DOTATOC) and for 24 with the DUO scheme (three cycles of [177Lu]Lu-DOTATOC alternated with two cycles of [90Y]Y-DOTATOC). Variations in terms of the ΔSUVmax of a maximum of three target lesions per patient (58 for MONO and 50 for DUO RLT) were assessed between baseline and 3 months post-RLT FDG PET. In patients with negative baseline FDG PET, the three most relevant lesions on [68Ga]Ga-DOTA-peptide PET were assessed and matched on post-RLT FDG PET, to check for any possible changes in FDG avidity. Thirty-five patients (62.5%) had at least one pathological FDG uptake at the baseline scans, but the number was reduced to 29 (52%) after RLT. In the patients treated with DUO-scheme RLT, 20 out of 50 lesions were FDG positive before therapy, whereas only 14 were confirmed after RLT (p = 0.03). Moreover, none of the 30 FDG-negative lesions showed an increased FDG uptake after RLT. The lesions of patients with pancreatic and CUP-NENs treated with the DUO scheme demonstrated a significant reduction in ΔSUVmax in comparison to those treated with MONO RLT (p = 0.03 and p = 0.04, respectively). Moreover, we found a mild positive correlation between the grading and ΔSUVmax in patients treated with the MONO scheme (r = 0.39, p < 0.02), while no evidence was detected for patients treated with the DUO scheme. Our results suggest that RLT, mostly with the DUO scheme, could be effective in changing NEN lesions’ glycometabolism, in particular, in patients affected by pancreatic and CUP-NENs, regardless of their Ki-67 index. Probably, associating [90Y]Y-labelled peptides, which have high energy emission and a crossfire effect, and [177Lu]Lu ones, characterized by a longer half-life and a safer profile for organs at risk, might represent a valid option in FDG-positive NENs addressed to RLT. Further studies are needed to validate our preliminary findings. In our opinion, FDG PET/CT should represent a potent tool for fully assessing a patient’s disease characteristics, both before and after RLT.

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90Y/177Lu-DOTATOC: From Preclinical Studies to Application in Humans

Cited by 23 publications

References 93 publications

Role of PSMA-ligands imaging in Renal Cell Carcinoma management: current status and future perspectives

Role of PSMA-ligands imaging in Renal Cell Carcinoma management: current status and future perspectives

DNA Damage Repair Defects and Targeted Radionuclide Therapies for Prostate Cancer: Does Mutation Really Matter? A Systematic Review

Glucose Metabolism Modification Induced by Radioligand Therapy with [177Lu]Lu/[90Y]Y-DOTATOC in Advanced Neuroendocrine Neoplasms: A Prospective Pilot Study within FENET-2016 Trial

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