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111In-Pentetreotide Scintigraphy Versus 68Ga-DOTATATE PET: Impact on Krenning Scores and Effect of Tumor Burden.

ABSTRACT: Eligibility for somatostatin receptor (SSTR) radionuclide therapy uses the qualitative Krenning score based on 111In-pentetreotide planar scintigraphy as was performed in the NETTER-1 trial. The purpose of this study was to determine the effect of using SSTR PET-based Krenning score in comparison to 111In-pentetreotide. Methods: This was a post hoc head-to-head comparison of 68Ga-DOTATATE-based and 111In-pentetreotide-based Krenning scores in 150 patients included in a prospective phase 2 study (NCT01967537). Patients were imaged using 68Ga-DOTATATE PET/CT, 111In-pentetreotide planar scintigraphy, and SPECT/CT within 1 wk. SSTR ligand uptake was graded using the Krenning score independently by 3 readers. Results: The detection rate of SSTR-expressing disease (Krenning scores 2-4) was 23%, 38%, and 72% with planar imaging, SPECT, and SSTR PET, respectively. The Krenning score was higher with SSTR PET (2.71 ± 1.74) than with planar imaging (0.75 ± 1.37; P < 0.001) or SPECT (1.23 ± 1.57; P < 0.001). In patients with a Krenning score of at least 3 on SSTR PET, the detection rate of planar imaging and SPECT was lower for lesions smaller than 2 cm than lesions 2 cm or larger: 15% and 24% versus 78% and 89%, respectively (P < 0.001). For lesions larger than 5 cm, Krenning scores between SSTR PET and 111In-pentetreotide were nearly equivalent. Lesion size did not have an impact on SSTR PET Krenning scores. Interreader agreement was higher for SSTR PET than for planar imaging or SPECT (0.79 vs. 0.67 and 0.50, respectively). Conclusion: SSTR PET results in higher Krenning scores than 111In-pentetreotide, particularly when lesions measured 2 cm or less. Small lesion size resulted in low Krenning scores using 111In-pentetreotide, but lesion size did not affect SSTR PET-based Krenning scores. The results of the NETTER-1 trial cannot be directly applied to patients with small lesions. Further study of peptide receptor radionuclide therapy in patients with small lesions negative on 111In-pentetreotide imaging and positive on SSTR PET is warranted.

SUBMITTER: Hope TA

PROVIDER: S-EPMC6735279 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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111In-Pentetreotide Scintigraphy Versus 68Ga-DOTATATE PET: Impact on Krenning Scores and Effect of Tumor Burden.

Hope Thomas A TA Calais Jeremie J Zhang Li L Dieckmann William W Millo Corina C

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20190308 9

Eligibility for somatostatin receptor (SSTR) radionuclide therapy uses the qualitative Krenning score based on 111In-pentetreotide planar scintigraphy as was performed in the NETTER-1 trial. The purpose of this study was to determine the effect of using SSTR PET-based Krenning score in comparison to 111In-pentetreotide. Methods: This was a post hoc head-to-head comparison of 68Ga-DOTATATE-based and 111In-pentetreotide-based Krenning scores in 15 ...[more]

PMID: 30850506

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Project description:BackgroundInflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([18F]FDG PET), [18F]FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover.ObjectivesThis study tested the efficacy of gallium-68-labeled DOTATATE (68Ga-DOTATATE), a somatostatin receptor subtype-2 (SST2)-binding PET tracer, for imaging atherosclerotic inflammation.MethodsWe confirmed 68Ga-DOTATATE binding in macrophages and excised carotid plaques. 68Ga-DOTATATE PET imaging was compared to [18F]FDG PET imaging in 42 patients with atherosclerosis.ResultsTarget SSTR2 gene expression occurred exclusively in "proinflammatory" M1 macrophages, specific 68Ga-DOTATATE ligand binding to SST2 receptors occurred in CD68-positive macrophage-rich carotid plaque regions, and carotid SSTR2 mRNA was highly correlated with in vivo 68Ga-DOTATATE PET signals (r = 0.89; 95% confidence interval [CI]: 0.28 to 0.99; p = 0.02). 68Ga-DOTATATE mean of maximum tissue-to-blood ratios (mTBRmax) correctly identified culprit versus nonculprit arteries in patients with acute coronary syndrome (median difference: 0.69; interquartile range [IQR]: 0.22 to 1.15; p = 0.008) and transient ischemic attack/stroke (median difference: 0.13; IQR: 0.07 to 0.32; p = 0.003). 68Ga-DOTATATE mTBRmax predicted high-risk coronary computed tomography features (receiver operating characteristics area under the curve [ROC AUC]: 0.86; 95% CI: 0.80 to 0.92; p < 0.0001), and correlated with Framingham risk score (r = 0.53; 95% CI: 0.32 to 0.69; p <0.0001) and [18F]FDG uptake (r = 0.73; 95% CI: 0.64 to 0.81; p < 0.0001). [18F]FDG mTBRmax differentiated culprit from nonculprit carotid lesions (median difference: 0.12; IQR: 0.0 to 0.23; p = 0.008) and high-risk from lower-risk coronary arteries (ROC AUC: 0.76; 95% CI: 0.62 to 0.91; p = 0.002); however, myocardial [18F]FDG spillover rendered coronary [18F]FDG scans uninterpretable in 27 patients (64%). Coronary 68Ga-DOTATATE PET scans were readable in all patients.ConclusionsWe validated 68Ga-DOTATATE PET as a novel marker of atherosclerotic inflammation and confirmed that 68Ga-DOTATATE offers superior coronary imaging, excellent macrophage specificity, and better power to discriminate high-risk versus low-risk coronary lesions than [18F]FDG. (Vascular Inflammation Imaging Using Somatostatin Receptor Positron Emission Tomography [VISION]; NCT02021188).

Project description:Background[68 Ga]Ga-DOTATATE PET/CT is now recognised as the most sensitive functional imaging modality for the diagnosis of well-differentiated neuroendocrine tumours (NET) and can inform treatment with peptide receptor radionuclide therapy with [177Lu]Lu-DOTATATE. However, somatostatin receptor (SSTR) expression is not unique to NET, and therefore, [68 Ga]Ga-DOTATATE PET/CT may have oncological application in other tumours. Molecular profiling of gastrointestinal stromal tumours that lack activating somatic mutations in KIT or PDGFRA or so-called 'wild-type' GIST (wtGIST) has demonstrated that wtGIST and NET have overlapping molecular features and has encouraged exploration of shared therapeutic targets, due to a lack of effective therapies currently available for metastatic wtGIST.AimsTo investigate (i) the diagnostic role of [68 Ga]Ga-DOTATATE PET/CT; and, (ii) to investigate the potential of this imaging modality to guide treatment with [177Lu]Lu-DOTATATE in patients with wtGIST.Methods[68 Ga]Ga-DOTATATE PET/CT was performed on 11 patients with confirmed or metastatic wtGIST and one patient with a history of wtGIST and a mediastinal mass suspicious for metastatic wtGIST, who was subsequently diagnosed with a metachronous mediastinal paraganglioma. Tumour expression of somatostatin receptor subtype 2 (SSTR2) using immunohistochemistry was performed on 54 tumour samples including samples from 8/12 (66.6%) patients who took part in the imaging study and 46 tumour samples from individuals not included in the imaging study.Results[68 Ga]Ga-DOTATATE PET/CT imaging was negative, demonstrating that liver metastases had lower uptake than background liver for nine cases (9/12 cases, 75%) and heterogeneous uptake of somatostatin tracer was noted for two cases (16.6%) of wtGIST. However, [68 Ga]Ga-DOTATATE PET/CT demonstrated intense tracer uptake in a synchronous paraganglioma in one case and a metachronous paraganglioma in another case with wtGIST.ConclusionsOur data suggest that SSTR2 is not a diagnostic or therapeutic target in wtGIST. [68 Ga]Ga-DOTATATE PET/CT may have specific diagnostic utility in differentiating wtGIST from other primary tumours such as paraganglioma in patients with sporadic and hereditary forms of wtGIST.

Project description:PurposeBone scintigraphy is the standard of reference in bone metastases in prostate cancer patients. However, new radiotracers employed in prostate-specific membrane antigen (PSMA)-ligands has led to the growing importance of PET/CT as diagnostic tool. The aim of our study was to investigate the difference between bone scan and PSMA-PET/CT for the detection of bone metastases in prostate cancer.MethodsThirty patients with bone metastases originating from prostate cancer were examined by 99mTc-MDP bone scan and 68Ga-PSMA-PET/CT within an average of 21 days. Bone scans were analyzed visually according to the number of lesions and using the software package ExiniBONE by Exini Diagnostics. PET/CT data was analyzed visually. Numbers of detected lesions were compared for the different methods for the whole patient and for different regions. In addition, results were compared to serum prostate-specific antigen (PSA), alkaline phosphatase (ALP), bone alkaline phosphatase (bALP), pro gastrin releasing peptide (pGRP) and eastern cooperative oncology group (ECOG) performance status.ResultsIn the bone scans, visual and semiautomatic lesion detection showed similar results with an average of 19.4 and 17.8 detected bone lesion per patient. However, in PSMA-PET/CT, on average double the numbers of lesions (40.0) were detected. The largest differences were found in the thorax and pelvis, which can be explained by the advantages of tomographic imaging. Bland-Altman analysis showed greater differences in patients with large numbers of bone metastases.ConclusionNo significant difference was found when using semiautomatic analysis compared to visual reading for bone scans. Fewer bone metastases were detected in bone scans than in PSMA-PET/CT. However, in none of our patients would the difference have led to clinical consequences. Therefore, it seems that for patients undergoing PSMA-PET/CT, there is no need to perform additional bone scans if the appropriate PET/CT protocols are applied.

Project description:BackgroundPrediction of [177Lu]Lu-HA-DOTATATE kidney and tumor uptake based on diagnostic [68Ga]Ga-HA-DOTATATE imaging would be a crucial step for precision dosing of [177Lu]Lu-HA-DOTATATE. In this study, the population pharmacokinetic (PK) differences between [177Lu]Lu-HA-DOTATATE and [68Ga]Ga-HA-DOTATATE were assessed and subsequently [177Lu]Lu-HA-DOTATATE was predicted based on [68Ga]Ga-HA-DOTATATE imaging.MethodsA semi-physiological nonlinear mixed-effects model was developed for [68Ga]Ga-HA-DOTATATE and [177Lu]Lu-HA-DOTATATE, including six compartments (representing blood, spleen, kidney, tumor lesions, other somatostatin receptor expressing organs and a lumped rest compartment). Model parameters were fixed based on a previously developed physiologically based pharmacokinetic model for [68Ga]Ga-HA-DOTATATE. For [177Lu]Lu-HA-DOTATATE, PK parameters were based on literature values or estimated based on scan data (four time points post-injection) from nine patients. Finally, individual [177Lu]Lu-HA-DOTATATE uptake into tumors and kidneys was predicted based on individual [68Ga]Ga-HA-DOTATATE scan data using Bayesian estimates. Predictions were evaluated compared to observed data using a relative prediction error (RPE) for both area under the curve (AUC) and absorbed dose. Lastly, to assess the predictive value of diagnostic imaging to predict therapeutic exposure, individual prediction RPEs (using Bayesian estimation) were compared to those from population predictions (using the population model).ResultsPopulation uptake rate parameters for spleen, kidney and tumors differed by a 0.29-fold (15% relative standard error (RSE)), 0.49-fold (15% RSE) and 1.43-fold (14% RSE), respectively, for [177Lu]Lu-HA-DOTATATE compared to [68Ga]Ga-HA-DOTATATE. Model predictions adequately described observed data in kidney and tumors for both peptides (based on visual inspection of goodness-of-fit plots). Individual predictions of tumor uptake were better (RPE AUC -40 to 28%) compared to kidney predictions (RPE AUC -53 to 41%). Absorbed dose predictions were less predictive for both tumor and kidneys (RPE tumor and kidney -51 to 44% and -58 to 82%, respectively). For most patients, [177Lu]Lu-HA-DOTATATE tumor accumulation predictions based on individual PK parameters estimated from diagnostic imaging outperformed predictions based on population parameters.ConclusionOur semi-physiological PK model indicated clear differences in PK parameters for [68Ga]Ga-HA-DOTATATE and [177Lu]Lu-HA-DOTATATE. Diagnostic images provided additional information to individually predict [177Lu]Lu-HA-DOTATATE tumor uptake compared to using a population approach. In addition, individual predictions indicated that many aspects, apart from PK differences, play a part in predicting [177Lu]Lu-HA-DOTATATE distribution.

Project description:Background and purposeMeningiomas express the somatostatin receptor (SSTR), which normal bone and brain lack. PET imaging with SSTR ligands such as 68 Ga-DOTATATE have been recently shown to aid in the imaging and identification of menginiomas. We hypothesize that 68 Ga-DOTATATE PET/CT in conjunction with MRI aids in radiation (RT) target volume delineation and evaluating treatment response.Materials and methodsNineteen patients with meningiomas underwent 68 Ga-DOTATATE PET/CT and MRI for RT planning and/or post-treatment follow-up. Meningiomas were grade I (n = 9) or not biopsied (n = 8) and frequently involved base of skull (n = 10). Ten (53%) patients received post-operative RT and 9 (47%) received fractaionted RT. In the subgroup that underwent both pre- and post-RT 68 Ga-DOTATATE PET as well as MRI (n = 10), ROVER (ABX GmbH, Radeberg, Germany) adaptive thresholding software was utilized to measure total lesion activity (mean and max) before and after treatment. Tumor volume based on MRI was calculated before and after treatment. Total lesion activity and tumor volume changes were compared using Wilcoxon signed rank test.Results68 Ga-DOTATATE PET/CT identified intraosseous (n = 4, 22%), falcine (n = 5, 26%) and satellite lesions (n = 3, 19%) and clarified the diagnosis of meningioma, resulting in a change in management in three patients. Mean total lesion activity decreased 14.7% (median), from pre to post-RT 68 Ga-DOTATATE PET [range 97-8.5% (25-75%),S = - 26.5, p = 0.0039]. Max total lesion activity decreased 36% (median) over the same period [range 105-15% (25-75%), S = - 26.5 p = 0.0039]. In contrast, meningioma volumes based on MRI measurements did not significantly change per RECIST criteria and Wilcoxon signed rank test (S = - 3, p = 0.7422).Conclusion68 Ga-DOTATATE PET/CT helped confirm suspected diagnoses and delineate target volumes particularly when lesions involved osseous structures and the falx. Mean and max total tumor 68 Ga-DOTATATE activity on PET/CT decreased at three months following RT despite stable tumor volumes on MRI. Future studies are warranted to (1) assess the sensitivity and specificity of 68 Ga-DOTATATE PET/CT, (2) evaluate the impact of 68 Ga-DOTATATE PET/CT-based planning on treatment outcomes, and (3) assess the prognostic significance of these post-treatment imaging changes.

Dataset Information

111In-Pentetreotide Scintigraphy Versus 68Ga-DOTATATE PET: Impact on Krenning Scores and Effect of Tumor Burden.

Publications

<sup>111</sup>In-Pentetreotide Scintigraphy Versus <sup>68</sup>Ga-DOTATATE PET: Impact on Krenning Scores and Effect of Tumor Burden.

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