Theranostic implications of molecular imaging phenotype of well-differentiated pulmonary carcinoid based on 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT

Zidan, Lamiaa; Iravani, Amir; Kong, Grace; Akhurst, Tim; Michael, Michael; Hicks, Rodney J.

doi:10.1007/s00259-020-04915-7

Cited by 31 publications

(34 citation statements)

References 44 publications

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“…Whilst a similar analysis in bronchial NENs has recently been published and demonstrated a significant proportion of patients with discordant lesions, a different scoring system was used, and the impact of dual PET scoring on overall survival was not reported. [24] This study suggests that patients with no avidity on either PET (analogous to P0) and patients with significant [ 18 F]FDG avid, [ 68 Ga]Ga-DOTATATE non-avid disease (analogous to P5) should not receive PRRT, which is concordant with our clinical experience. Further investigations into a molecular imaging-led paradigm for treatment selection may impact care for patients with bronchial NEN (e.g.…”

Section: Discussionsupporting

confidence: 85%

“…The current study treats the P2-4 group ( show a link between different dual PET imaging phenotypes and molecular changes in bronchial NENs [26]. Finally, the aetiology and significance of disease that is non-avid on both [ 68 Ga]Ga-DOTATATE and [ 18 F]FDG PET remains to be determined [24].…”

Section: Discussionmentioning

confidence: 86%

“…The current findings (particularly the interplay between Ki-67, NETPET score and prognosis) should ideally be confirmed by a prospective study. Finally, we note that we included bronchial NENs of all histologies (from typical carcinoid to small cell neuroendocrine carcinoma), as opposed to a recent study which enrolled only patients with typical and atypical carcinoid [25]. This inclusion allowed us to demonstrate the value of dual PET imaging and its correlation to highgrade histologies; our results remained significant for NETPET score alone on restriction of the cohort to typical and atypical carcinoid histologies (data not shown).…”

Section: Discussionmentioning

confidence: 96%

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Dual PET Imaging in Bronchial Neuroendocrine Neoplasms: The NETPET Score as a Prognostic Biomarker

et al. 2021

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Background: PET scans using [ 18 F]FDG and somatostatin receptor imaging agents are both used in imaging of neuroendocrine neoplasms (NENs). We have suggested the "NETPET score", utilizing uptake of both PET tracers, as a prognostic biomarker in NENs. We previously demonstrated the effectiveness of the NETPET score in gastroenteropancreatic (GEP) NENs. Its prognostic relevance in bronchial NENs remains undetermined. Methods: This is a retrospective multicentre study (2011-2018) assessing patients who had advanced bronchial NEN and who underwent both [ 18 F]FDG and [ 68 Ga]Ga-DOTATATE PET within 60 days of each other. The NETPET score was assigned by experienced nuclear medicine physicians and compared with other clinical data such as WHO grade. The primary outcome was overall survival (OS); NETPET score and other prognostic variables were analysed using univariate and multivariate analyses by the Cox proportional-hazards model. Results: Thirty-eight patients were included for review. The NETPET score and histology were significantly correlated with OS in univariate analyses (p=0.003, p=0.01). On multivariate analysis, only the NETPET score remained significant (p=0.03). The NETPET score was significantly associated with histological grade (p=0.006, chi-squared test). Conclusion: The NETPET score is a prognostic biomarker in bronchial NENs as well as GEPNENs. Whilst it needs to be validated in prospective studies, it holds significant promise as a biomarker for a wide range of NENs.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 96%

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Dual PET Imaging in Bronchial Neuroendocrine Neoplasms: The NETPET Score as a Prognostic Biomarker

et al. 2021

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“…Well-differentiated neuroendocrine tumours (NET) are characterised by an overexpression of somatostatin receptors (SSR) on the cell surface [1] which serve as a target for radiolabelled somatostatin analogues (SSA) used for both diagnostics and therapy (theranostics) [2,3]. Considering improved detection rates especially in early disease stages, SSR-targeted combined positron emission tomography/computer tomography (PET/CT) contributes to the increasing incidence of this overall heterogeneous group of neoplasms [4].…”

Section: Introductionmentioning

confidence: 99%

Dosimetry and optimal scan time of [18F]SiTATE-PET/CT in patients with neuroendocrine tumours

Beyer

Gosewisch

Lindner

et al. 2021

Eur J Nucl Med Mol Imaging

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Purpose Radiolabelled somatostatin analogues targeting somatostatin receptors (SSR) are well established for combined positron emission tomography/computer tomography (PET/CT) imaging of neuroendocrine tumours (NET). [18F]SiTATE has recently been introduced showing high image quality, promising clinical performance and improved logistics compared to the clinical reference standard 68Ga-DOTA-TOC. Here we present the first dosimetry and optimal scan time analysis. Methods Eight NET patients received a [18F]SiTATE-PET/CT (250 ± 66 MBq) with repeated emission scans (10, 30, 60, 120, 180 min after injection). Biodistribution in normal organs and SSR-positive tumour uptake were assessed. Dosimetry estimates for risk organs were determined using a combined linear-monoexponential model, and by applying 18F S-values and reference target masses for the ICRP89 adult male or female (OLINDA 2.0). Tumour-to-background ratios were compared quantitatively and visually between different scan times. Results After 1 h, normal organs showed similar tracer uptake with only negligible changes until 3 h post-injection. In contrast, tracer uptake by tumours increased progressively for almost all types of metastases, thus increasing tumour-to-background ratios over time. Dosimetry resulted in a total effective dose of 0.015 ± 0.004 mSv/MBq. Visual evaluation revealed no clinically relevant discrepancies between later scan times, but image quality was rated highest in 60 and 120 min images. Conclusion [18F]SiTATE-PET/CT in NET shows overall high tumour-to-background ratios from 60 to 180 min after injection and an effective dose comparable to 68Ga-labelled alternatives. For clinical use of [18F]SiTATE, the best compromise between image quality and tumour-to-background contrast is reached at 120 min, followed by 60 min after injection.

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“…PRRT is an effective treatment option for patients with advanced GEP NET with sufficient SSR expression who progressed on SSA (4,7). We have recently reported that only a proportion of lung NET expresses SSR at sufficient levels to potentially benefit from PRRT (17). Although lung NETs were not included in the NETTER-1 trial, limited clinical studies have shown promising results (6,7).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of ¹⁷⁷Lu-DOTATATE in Lung Neuroendocrine Tumors: A Bicenter study

et al. 2021

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To assess the efficacy and safety of 177 Lu-DOTATATE in patients with somatostatin receptor (SSR) positive lung neuroendocrine tumor (NET).Methods: This is a retrospective review of the outcome of patients with typical carcinoid (TC) and atypical carcinoid (AC), treated with 177 Lu-DOTATATE at two ENETS Centres of Excellence. Morphological imaging (RECIST 1.1) and 68 Ga-DOTATATE PET/CT responses were assessed at 3 months after completion of 177 Lu-DOTATATE. Concordance between two response assessment methods was evaluated by Kappa statistics. Progression-free survival (PFS) and overall survival (OS) was estimated by Kaplan-Meier analysis and compared by Log-rank test. Treatment-related adverse events (AEs) were graded based on CTCAE version 5.Results: Of 48 patients (median age, 63 years, 13 female), 43 (90%) had AC and 5 (10%) TC. Almost all patients (47, 98%) were treated due to progression. Majority (40, 83%) received somatostatin analogs and 10 patients (20%) had prior everolimus, chemotherapy or both. All patients had high SSR expression (≥ modified Krenning score 3) on pre-treatment 68 Ga-DOTATATE PET/CT. Patients received a median 4 (range 1-4) cycles of 177 Lu-DOTATATE (33% with concurrent radiosensitizing chemotherapy) to a median cumulative activity of 27GBq (range 6-43GBq). At median follow-up of 42 months, the median PFS and OS were 23 months (95% CI 18-28 months) and 59 months (95% CI 50-not reached [NR]), respectively.Of 40 patients with RECIST-measurable disease and 39 patients with available 68 Ga-DOTATATE PET/CT response categories were: partial response, 20% (95% CI 10-35%) and 44% (95% CI 30-59%); stable disease, 68% (95% CI 52-80%) and 44% (95% CI 30-59%) and progressive disease 12% (95% CI 5-27%) by both, respectively. There was a moderate concordance between response categories by RECIST and 68 Ga-DOTATATE PET/CT, weighted Kappa of 0.51 (95% CI 0.21-0.68). Of patients with stable disease by RECIST, those with partial response on 68 Ga-DOTATATE PET/CT had longer OS compared to those with no response, NR vs 52 months (95% CI 28-64), HR 0.2 (95% CI 0.1-0.6), p 0.001. Most grade 3/4 AEs were reversible and the most common was lymphopenia (14%) with no incidence of myelodysplasia/leukemia.

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Theranostic implications of molecular imaging phenotype of well-differentiated pulmonary carcinoid based on 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT

Cited by 31 publications

References 44 publications

Dual PET Imaging in Bronchial Neuroendocrine Neoplasms: The NETPET Score as a Prognostic Biomarker

Dual PET Imaging in Bronchial Neuroendocrine Neoplasms: The NETPET Score as a Prognostic Biomarker

Dosimetry and optimal scan time of [18F]SiTATE-PET/CT in patients with neuroendocrine tumours

Efficacy and Safety of ¹⁷⁷Lu-DOTATATE in Lung Neuroendocrine Tumors: A Bicenter study

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Theranostic implications of molecular imaging phenotype of well-differentiated pulmonary carcinoid based on 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT

Cited by 31 publications

References 44 publications

Dual PET Imaging in Bronchial Neuroendocrine Neoplasms: The NETPET Score as a Prognostic Biomarker

Dual PET Imaging in Bronchial Neuroendocrine Neoplasms: The NETPET Score as a Prognostic Biomarker

Dosimetry and optimal scan time of [18F]SiTATE-PET/CT in patients with neuroendocrine tumours

Efficacy and Safety of 177Lu-DOTATATE in Lung Neuroendocrine Tumors: A Bicenter study

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Efficacy and Safety of ¹⁷⁷Lu-DOTATATE in Lung Neuroendocrine Tumors: A Bicenter study