Background
Segmenting the whole-body somatostatin receptor-expressing tumour volume (SRETVwb) on positron emission tomography/computed tomography (PET/CT) images is highly time-consuming but has ...shown value as an independent prognostic factor for survival. An automatic method to measure SRETVwb could improve disease status assessment and provide a tool for prognostication. This study aimed to develop an artificial intelligence (AI)-based method to detect and quantify SRETVwb and total lesion somatostatin receptor expression (TLSREwb) from
68
GaGa-DOTA-TOC/TATE PET/CT images.
Methods
A UNet3D convolutional neural network (CNN) was used to train an AI model with
68
GaGa-DOTA-TOC/TATE PET/CT images, where all tumours were manually segmented with a semi-automatic method. The training set consisted of 148 patients, of which 108 had PET-positive tumours. The test group consisted of 30 patients, of which 25 had PET-positive tumours. Two physicians segmented tumours in the test group for comparison with the AI model.
Results
There were good correlations between the segmented SRETVwb and TLSREwb by the AI model and the physicians, with Spearman rank correlation coefficients of
r
= 0.78 and
r
= 0.73, respectively, for SRETVwb and
r
= 0.83 and
r
= 0.81, respectively, for TLSREwb. The sensitivity on a lesion detection level was 80% and 79%, and the positive predictive value was 83% and 84% when comparing the AI model with the two physicians.
Conclusion
It was possible to develop an AI model to segment SRETVwb and TLSREwb with high performance. A fully automated method makes quantification of tumour burden achievable and has the potential to be more widely used when assessing PET/CT images.
Given the rising pervasiveness of melanocortin-1 receptor (MC1-R) positive melanoma malignum (MM) and pertinent metastases, radiolabelled receptor-affine alpha-melanocyte stimulating hormone-analogue ...(α-MSH analogue) imaging probes would be of crucial importance in timely tumor diagnostic assessment. Herein we aimed at investigating the biodistribution and the MM targeting potential of newly synthesized 213Bi-conjugated MC1-R specific peptide-based radioligands with the establishment of MC1-R overexpressing MM preclinical model. DOTA-conjugated NAP, -HOLD, -FOLD, -and MARSamide were labelled with 213Bi. Ex vivo biodistribution studies were conducted post-administration of 3.81 ± 0.32 MBq 213BiBi-DOTA conjugated deriva-tives into twenty B16-F10 tumor-bearing C57BL/6 J and healthy mice. Organ Level Internal Dose Assessment (OLINDA) and IDAC-Dose were used to calculate translational data-based absorbed radiation dose in human organs. Moderate or low %ID/g uptake of 213BiBi-DOTA conjugated NAP, -HOLD, -and MARSamide and significantly increased 213BiBi-DOTA-FOLDamide accumulation was observed in the thoracic and abdominal organs (p ≤ 0.01). High 213BiBi-DOTA-NAP (%ID/g:3.76 ± 0.96), -and FOLDamide (%ID/g:3.28 ± 0.95) tumor tracer activity confirmed their MC1-R-affinity. The bladder wall received the highest radiation absorbed dose followed by the kidneys (bladder wall: 1.95·10-2 and 8.97·10-2 mSv/MBq; kidneys: 7.47·10-3 vs. 5.88·10-2 mSv/MBq measured by IDAC and OLINDA; respectively) indicating the suitability of the NAPamide derivative for clinical use. These novel 213BiBi-DOTA-linked peptide probes displaying meaningful MC1-R affinity could be promising molecular probes in MM imaging.
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•213BiBi-DOTA-linked peptide probes display meaningful MC1-R affinity.•213BiBi-DOTA-NAPamide is a promising molecular probe in melanoma imaging.•213Bi-labelled NAPamide could be a potent weapon in targeted melanoma treatment.
Somatostatin receptor imaging constitutes an integral part in neuroendocrine tumor visualization and should, because of its vastly superior performance, use
Ga-DOTA-somatostatin analogue-PET/computed ...tomography rather than scintigraphy; it is particularly valuable for detecting metastases to lymph nodes, bone, peritoneum, and liver, which may be missed by morphologic imaging.
FDG-PET/computed tomography is better suited for G3 and high-G2 neuroendocrine tumors.
FDG-PET/computed tomography provides prognostic information. Alternative available PET tracers are
F-DOPA and
C-5-hydroxytryptophan. To take full advantage of the technique PET/computed tomography should include diagnostic intravenous contrast-enhanced computed tomography. PET/MRI is currently mainly investigational.
68Ga-labeled dodecane tetraacetic acid tyrosine-3-octreotate (68Ga-DOTA-TATE) and 177Lu-labeled DOTA-TATE (177Lu-DOTA-TATE) are radiolabeled somatostatin analogs used to detect or treat ...neuroendocrine tumors. They are administered separately for either diagnostic or therapeutic purposes but little experimental data for their biokinetics are measured simultaneously in the same biological model. By co-administering 68Ga-DOTA-TATE and 177Lu-DOTA-TATE in three laboratory mice bearing two Institute for Medical Research-32 (IMR32) tumor xenografts expressing different levels of somatostatin receptors (SSTRs) on their shoulders and imaging both 68Ga and 177Lu simultaneously, we investigated the relationship between the uptake of 68Ga-DOTA-TATE and 177Lu-DOTA-TATE in organs and tumors. In addition, using the percent of injected activity (%IA) values of 68Ga-DOTA-TATE at 0 h and 4 h, we investigated the correlation between 68Ga-DOTA-TATE %IA and the time-integrated activity coefficients (TIACs) of 177Lu-DOTA-TATE to estimate the organ-based and tumor-based doses of 177Lu-DOTA-TATE. The results showed that the extrapolated clearance time of 68Ga-DOTA-TATE linearly correlated with the TIACs of 177Lu-DOTA-TATE in the IMR32-SSTR2 tumor, kidneys, brain, heart, liver, stomach, and remainder body. The extrapolated %IA value at 0 h of 68Ga-DOTA-TATE linearly correlated with the TIACs of 177Lu-DOTA-TATE in the IMR32 tumor and lungs. In our murine study, both kidneys and lungs were organs that showed high absorbed doses of 177Lu-DOTA-TATE.
The aim of this paper was to investigate correlations between pre- therapeutic
GaGa-DOTA-TOC uptake and absorbed dose to tumours from therapy with
LuLu-DOTA-TATE.
This retrospective study included ...301 tumours from 54 GEP-NET patients. The tumours were segmented on pre-therapeutic
GaGa-DOTA-TOC PET/CT, and post-therapy
LuLu-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
and SUV
were measured from the PET images. A linear absorbed-dose prediction model was formed with SUV
as the independent variable, and the accuracy was tested with a split 70-30 training-test set.
Mean SUV
and SUV
from
GaGa-DOTA-TOC PET was 24.0 (3.6-84.4) and 41.0 (6.7-146.5), and the mean absorbed dose from
LuLu-DOTA-TATE was 26.9 Gy (2.4-101.9). A linear relationship between SUV
and
LuLu-DOTA-TATE activity concentration at 24 h post injection was found (R
= 0.44,
< 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.
There was a high inter- and intra-patient variability in tumour measurements, both for
GaGa-DOTA-TOC SUVs and absorbed doses from
LuLu-DOTA-TATE. Depending on the required accuracy,
GaGa-DOTA-TOC PET imaging may estimate the
LuLu-DOTA-TATE uptake. However, there could be a high variance between predicted and actual absorbed doses.
To evaluate the cost-effectiveness of 177LuLu-DOTA-TATE versus relevant comparators for the treatment of neuroendocrine tumours located in the gastrointestinal tract (GI-NETs) and the pancreas ...(P-NETs).
A three-state partitioned survival model was developed to perform a cost-utility analysis of 177LuLu-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 177LuLu-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 177LuLu-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).
In GI-NETs, the incremental cost-effectiveness ratio (ICER) of 177LuLu-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 177LuLu-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.
At a willingness to pay threshold of £30,000, 177LuLu-DOTA-TATE is likely to be a cost-effective treatment option for GI-NET and P-NET patients versus relevant treatment comparators (NHS perspective).
•A three-state partitioned survival model of GEP-NET patients was developed.•Base case ICERs for 177LuLu-DOTA-TATE were under £30,000 per QALY for all comparators.•177LuLu-DOTA-TATE is cost-effective for the treatment of GEP-NETs from a NICE perspective.
As the first radiopharmaceutical for Peptide Receptor Radionuclide Therapy (PRRT), Lutathera
was approved by the EMA in 2017 and the FDA in 2018 for the treatment of somatostatin receptor (SSTR) ...positive gastroenteropancreatic neuroendocrine tumors. Using the concept of PRRT, Lutathera
combines the radionuclide
Lu with the somatostatin analogue DOTA-TATE, thus delivering ionizing radiation specifically to tumor cells expressing somatostatin receptors. As a result, DNA single- and double-strand breaks are provoked, in case of double-strand breaks leading to cell death of the tumor and its SSTR-positive lesions.
In the past few years, the introduction of novel PET tracers labelled with (68)Ga has changed the diagnostic approach to neuroendocrine tumours (NET) in specialized centres. Although somatostatin ...analogue tracers labelled with (111)In have represented the gold standard imaging modality for NET detection in past decades, the advantages offered by both labelling somatostatin analogues with (68)Ga and using PET/CT tomography for image acquisition, account for the increasing use of these tracers in clinical practice. There are an increasing number of reports of the higher accuracy of (68)Ga-DOTA peptide PET/CT for the detection of NET lesions as compared to morphological imaging procedures and somatostatin receptor scintigraphy. Moreover, the use of (68)Ga-DOTA peptides offers the possibility to noninvasively evaluate NET cells for the presence of somatostatin receptor expression, with direct therapeutic implications. Several practical advantages also favour the use of (68)Ga-DOTA peptides including the relatively easy and economic synthesis process and the fact that (68)Ga labelling can be performed in centres without an on-site cyclotron. We describe the advantages and limitations of (68)Ga-DOTA peptide PET/CT imaging for the assessment of gastroenteropancreatic NET referring to the available literature as well as to our experience, and finally highlight potential future perspectives.
The present retrospective analysis sought to compare the relative diagnostic efficacy of
GaGa-DOTA-FAPI-04 to that of
FFDG PET/CT as a means of detecting bone metastases in patients with a range of ...cancer types.
In total, 30 patients with bone metastases associated with different underlying malignancies were retrospectively enrolled. All patients had undergone
GaGa-DOTA-FAPI-04 and
FFDG PET/CT, and the McNemar test was used to compare the relative diagnostic performance of these two imaging modalities. The maximum standard uptake value (SUVmax) was used to quantify radiotracer uptake by metastatic lesions, with the relative uptake associated with these two imaging strategies being compared
the Mann-Whitney U test. The cohort was further respectively divided into two (osteolytic and osteoblastic bone metastases) and three clinical subgroups (lung cancer, thyroid cancer, and liver cancer).
GaGa-DOTA-FAPI-04 PET/CT was found to be significantly more sensitive as a means of diagnosing bone metastases relative to
FFDG PET/CT (109/109 100%
89/109 81.7%; P< 0.01), consistent with the significantly increased uptake of
GaGa-DOTA-FAPI-04 by these metastatic lesions relative to that of
FFDG (n=109, median SUVmax, 9.1
. 4.5; P< 0.01).
GaGa-DOTA-FAPI-04 accumulation was significantly higher than that of
FFDG in both osteolytic (n=66, median SUVmax, 10.6
6.1; P < 0.01), and osteoblastic metastases (n=43, median SUVmax, 7.7
3.7; P < 0.01).
GaGa-DOTA-FAPI-04 uptakes were significantly higher than that of
FFDG in bone metastases from lung cancer (n = 62, median SUVmax, 10.7
5.2; P < 0.01), thyroid cancer (n = 18, median SUVmax, 5.65
2.1; P < 0.01) and liver cancer (n = 12, median SUVmax, 5.65
3.05; P < 0.01). However,
GaGa-DOTA-FAPI-04 detected 10 false-positive lesions, while only 5 false-positive were visualized by
FFDG PET/CT.
GaGa-DOTA-FAPI-04 PET/CT exhibits excellent diagnostic performance as a means of detecting bone metastases, and is superior to
FFDG PET/CT in this diagnostic context. Furthermore,
GaGa-DOTA-FAPI-04 tracer uptake levels are higher than those of
FFDG for most bone metastases. However, owing to the potential for false-positive bone lesions, it is critical that physicians interpret all CT findings with caution to ensure diagnostic accuracy.