Dataset Information

Correlations between [⁶⁸Ga]Ga-DOTA-TOC Uptake and Absorbed Dose from [¹⁷⁷Lu]Lu-DOTA-TATE.

ABSTRACT:

Purpose

The aim of this paper was to investigate correlations between pre- therapeutic [⁶⁸Ga]Ga-DOTA-TOC uptake and absorbed dose to tumours from therapy with [¹⁷⁷Lu]Lu-DOTA-TATE.

Methods

This retrospective study included 301 tumours from 54 GEP-NET patients. The tumours were segmented on pre-therapeutic [⁶⁸Ga]Ga-DOTA-TOC PET/CT, and post-therapy [¹⁷⁷Lu]Lu-DOTA-TATE SPECT/CT images, using a fixed 40% threshold. The SPECT/CT images were used for absorbed dose calculations by assuming a linear build-up from time zero to day one, and mono-exponential wash-out after that. Both SUV_mean and SUV_max were measured from the PET images. A linear absorbed-dose prediction model was formed with SUV_mean as the independent variable, and the accuracy was tested with a split 70-30 training-test set.

Results

Mean SUV_mean and SUV_max from [⁶⁸Ga]Ga-DOTA-TOC PET was 24.0 (3.6-84.4) and 41.0 (6.7-146.5), and the mean absorbed dose from [¹⁷⁷Lu]Lu-DOTA-TATE was 26.9 Gy (2.4-101.9). A linear relationship between SUV_mean and [¹⁷⁷Lu]Lu-DOTA-TATE activity concentration at 24 h post injection was found (R² = 0.44, p < 0.05). In the prediction model, a root mean squared error and a mean absolute error of 1.77 and 1.33 Gy/GBq, respectively, were found for the test set.

Conclusions

There was a high inter- and intra-patient variability in tumour measurements, both for [⁶⁸Ga]Ga-DOTA-TOC SUVs and absorbed doses from [¹⁷⁷Lu]Lu-DOTA-TATE. Depending on the required accuracy, [⁶⁸Ga]Ga-DOTA-TOC PET imaging may estimate the [¹⁷⁷Lu]Lu-DOTA-TATE uptake. However, there could be a high variance between predicted and actual absorbed doses.

SUBMITTER: Bruvoll R

PROVIDER: S-EPMC9954147 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Correlations between [<sup>68</sup>Ga]Ga-DOTA-TOC Uptake and Absorbed Dose from [<sup>177</sup>Lu]Lu-DOTA-TATE.

Bruvoll Ragnar R Blakkisrud Johan J Mikalsen Lars Tore LT Connelly James J Stokke Caroline C

Cancers 20230210 4

<h4>Purpose</h4>The aim of this paper was to investigate correlations between pre- therapeutic [<sup>68</sup>Ga]Ga-DOTA-TOC uptake and absorbed dose to tumours from therapy with [<sup>177</sup>Lu]Lu-DOTA-TATE.<h4>Methods</h4>This retrospective study included 301 tumours from 54 GEP-NET patients. The tumours were segmented on pre-therapeutic [<sup>68</sup>Ga]Ga-DOTA-TOC PET/CT, and post-therapy [<sup>177</sup>Lu]Lu-DOTA-TATE SPECT/CT images, using a fixed 40% threshold. The SPECT/CT images were u ...[more]

PMID: 36831477

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Project description:PurposeIn the characterization of severe lung diseases, early detection of specific inflammatory cells could help to monitor patients' response to therapy and increase chances of survival. Macrophages contribute to regulating the resolution and termination of inflammation and have increasingly been of interest for targeted therapies. [68Ga]Ga-DOTA-TATE is an established clinical radiopharmaceutical targeting somatostatin receptor subtype 2 (SSTR 2). Since activated macrophages (M1) overexpress SSTR 2, the aim of this study was to investigate the applicability of [68Ga]Ga-DOTA-TATE for positron emission tomography (PET) imaging of M1 macrophages in pulmonary inflammation.MethodsInflammation in the pig lungs was induced by warm saline lavage followed by injurious ventilation in farm pigs (n = 7). Healthy pigs (n = 3) were used as control. A 60-min dynamic PET scan over the lungs was performed after [68Ga]Ga-DOTA-TATE injection and [18F]FDG scan was executed afterward for comparison. The uptake of both tracers was assessed as mean standardized uptake values (SUVmean) 30-60-min post-injection. The PET scans were followed by computed tomography (CT) scans, and the Hounsfield units (HU) were quantified of the coronal segments. Basal and apical segments of the lungs were harvested for histology staining. A rat lung inflammation model was also studied for tracer specificity using lipopolysaccharides (LPS) by oropharyngeal aspiration. Organ biodistribution, ex vivo autoradiography (ARG) and histology samples were conducted on LPS treated, octreotide induced blocking and control healthy rats.ResultsThe accumulation of [68Ga]Ga-DOTA-TATE on pig lavage model was prominent in the more severely injured dorsal segments of the lungs (SUVmean = 0.91 ± 0.56), compared with control animals (SUVmean = 0.27 ± 0.16, p < 0.05). The tracer uptake corresponded to the damaged areas assessed by CT and histology and were in line with HU quantification. The [68Ga]Ga-DOTA-TATE uptake in LPS treated rat lungs could be blocked and was significantly higher compared with control group.ConclusionThe feasibility of the noninvasive assessment of tissue macrophages using [68Ga]Ga-DOTA-TATE/PET was demonstrated in both porcine and rat lung inflammation models. [68Ga]Ga-DOTA-TATE has a great potential to be used to study the role and presence of macrophages in humans in fight against severe lung diseases.

Project description:BackgroundSince it was first approved in Europe in 2016, the gallium-68 (68Ga) radiopharmaceutical [68Ga]Ga-DOTA-TOC has been widely used for imaging of somatostatin receptor (SSTR) positive tumours using positron emission tomography-computed tomography (PET/CT). Significant patient benefits have been reported, so its use is rapidly increasing. However, few studies have been published regarding occupational doses to nuclear medicine personnel handling this radiopharmaceutical, despite its manual usage at low distances from the skin and the beta-emission decay scheme, which may result in an increased absorbed dose to their hands. In this context, this study aims to analyse the occupational exposure during the administration of [68Ga]Ga-DOTA-TOC for PET/CT imaging. For this purpose, extremity, eye lens and whole-body dosimetry in terms of Hp(0.07), Hp(3) and Hp(10), respectively, was conducted on six workers with both thermoluminescent dosimeters, and personal electronic dosimeters.ResultsThe non-dominant hand is more exposed to radiation than the dominant hand, with the thumb and the index fingertip being the most exposed sites on this hand. Qualitative analysis showed that when no shielding is used during injection, doses increase significantly more in the dominant than in the non-dominant hand, so the use of shielding is strongly recommended. While wrist dosimeters may significantly underestimate doses to the hands, placing a ring dosimeter at the base of the ring or middle finger of the non-dominant hand may give a valuable estimation of maximum doses to the hands if at least a correction factor of 5 is applied. Personal equivalent doses for the eyes did not result in measurable values (i.e., above the lowest detection limit) for almost all workers. The extrapolated annual dose estimations showed that there is compliance with the annual dose limits during management of [68Ga]Ga-DOTA-TOC for diagnostics with PET in the hospital included in this study.ConclusionsImaging with [68Ga]Ga-DOTA-TOC is a safe process for the workers performing the administration of the radiopharmaceutical, including intravenous injection to the patient and the pre- and post-activity control, as it is highly unlikely that annual dose limits will be exceeded if good working practices and shielding are used.

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Project description:AimTo evaluate the cost-effectiveness of [177Lu]Lu-DOTA-TATE versus relevant comparators for the treatment of neuroendocrine tumours located in the gastrointestinal tract (GI-NETs) and the pancreas (P-NETs).Materials and methodsA three-state partitioned survival model was developed to perform a cost-utility analysis of [177Lu]Lu-DOTA-TATE versus standard of care (high dose Octreotide LAR), everolimus and sunitinib. Effectiveness data for SoC, everolimus and sunitinib were obtained from published Kaplan-Meier survival curves. Given a lack of head-to-head effectiveness data, matching adjusted indirect comparisons (MAICs) were performed to population-adjust [177Lu]Lu-DOTA-TATE survival data based on prognostic factors and derive estimates of relative effectiveness. Health state utilities were estimated from real-world evidence. Drug acquisition costs were taken from nationally published sources (BNF, NICE), and administration costs were based on treatment protocols in [177Lu]Lu-DOTA-TATE studies, combined with nationally published unit costs (PSSRU, DoH reference costs). Incidence of adverse events were estimated using published sources. A discount rate of 3.5% was applied to both utilities and costs, and deterministic and probabilistic sensitivity analyses were performed. Costs were included from an NHS perspective and presented in 2017/18 GBP (and PPP Euros for base case).ResultsIn GI-NETs, the incremental cost-effectiveness ratio (ICER) of [177Lu]Lu-DOTA-TATE compared to SoC and everolimus was £26,528 (€27,672) and £24,145 (€25,186) per QALY, respectively. In P-NETs, the ICER of [177Lu]Lu-DOTA-TATE compared to SoC was £22,146 (€23,101) or £28,038 (€29,251) dependent on matched population, and £21,827 (€22,766) and £15,768 (€16,445) compared to everolimus and sunitinib, respectively.ConclusionsAt a willingness to pay threshold of £30,000, [177Lu]Lu-DOTA-TATE is likely to be a cost-effective treatment option for GI-NET and P-NET patients versus relevant treatment comparators (NHS perspective).

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Dataset Information

Correlations between [⁶⁸Ga]Ga-DOTA-TOC Uptake and Absorbed Dose from [¹⁷⁷Lu]Lu-DOTA-TATE.

Purpose

Methods

Results

Conclusions

Publications

Correlations between [<sup>68</sup>Ga]Ga-DOTA-TOC Uptake and Absorbed Dose from [<sup>177</sup>Lu]Lu-DOTA-TATE.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Correlations between [68Ga]Ga-DOTA-TOC Uptake and Absorbed Dose from [177Lu]Lu-DOTA-TATE.

Purpose

Methods

Results

Conclusions

Publications

Correlations between [<sup>68</sup>Ga]Ga-DOTA-TOC Uptake and Absorbed Dose from [<sup>177</sup>Lu]Lu-DOTA-TATE.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Correlations between [⁶⁸Ga]Ga-DOTA-TOC Uptake and Absorbed Dose from [¹⁷⁷Lu]Lu-DOTA-TATE.