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(68)Ga-DOTATOC PET and gene expression profile in patients with neuroendocrine carcinomas: strong correlation between PET tracer uptake and gene expression of somatostatin receptor subtype 2.

ABSTRACT: Somatostatin receptor expression on both protein and gene expression level was compared with in vivo (68)Ga-DOTATOC PET/CT in patients with neuroendocrine carcinomas (NEC). Twenty-one patients with verified NEC who underwent a (68)Ga-DOTATOC PET/CT between November 2012 and May 2014, were retrospectively included. By real-time polymerase chain reaction, we quantitatively determined the gene expression of several genes and compared with (68)Ga-DOTATOC PET uptake. By immunohistochemistry we qualitatively studied the expression of assorted proteins in NEC. The median age at diagnosis was 68 years (range 41-84) years. All patients had WHO performance status 0-1. Median Ki67 index was 50% (range 20-100%). Gene expression of somatostatin receptor subtype (SSTR) 2 and Ki67 were both positively correlated to the (68)Ga-DOTATOC uptake (r=0.89; p<0.0001 and r=0.5; p=0.021, respectively). Furthermore, SSTR2 and SSTR5 gene expression were strongly and positively correlated (r=0.57; p=0.006). This study as the first verifies a positive and close correlation of (68)Ga-DOTATOC uptake and gene expression of SSTR2 in NEC. SSTR2 gene expression has a stronger correlation to (68)Ga-DOTATOC uptake than SSTR5. In addition, the results indicate that the gene expression levels of SSTR2 and SSTR5 at large follow one another.

SUBMITTER: Olsen IH

PROVIDER: S-EPMC4749505 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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(68)Ga-DOTATOC PET and gene expression profile in patients with neuroendocrine carcinomas: strong correlation between PET tracer uptake and gene expression of somatostatin receptor subtype 2.

Olsen Ingrid H IH Langer Seppo W SW Federspiel Birgitte H BH Oxbøl Jytte J Loft Annika A Berthelsen Anne Kiil AK Mortensen Jann J Oturai Peter P Knigge Ulrich U Kjær Andreas A

American journal of nuclear medicine and molecular imaging 20160128 1

Somatostatin receptor expression on both protein and gene expression level was compared with in vivo (68)Ga-DOTATOC PET/CT in patients with neuroendocrine carcinomas (NEC). Twenty-one patients with verified NEC who underwent a (68)Ga-DOTATOC PET/CT between November 2012 and May 2014, were retrospectively included. By real-time polymerase chain reaction, we quantitatively determined the gene expression of several genes and compared with (68)Ga-DOTATOC PET uptake. By immunohistochemistry we qualit ...[more]

PMID: 27069766

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Project description:68Ga-DOTATOC, a somatostatin receptor-targeted ligand, has been used clinically in Europe over the past decade for imaging neuroendocrine tumors (NETs). It appears to be quite sensitive and effective for clinical management decision making. This metaanalysis summarizes the efficacy of 68Ga-DOTATOC for several distinct indications and is intended to support approval of this agent by the U.S. Food and Drug Administration. Methods: The major electronic medical databases were searched for relevant papers over the period from January 2001 to November 2015. Papers were selected for review in 3 categories: clinical trials that reported sensitivity and specificity, comparison studies with 111In-octreotide, and change of management studies. All the eligible papers underwent Quality Assessment of Diagnostic Accuracy Studies (QUADAS) assessment, which was useful in the final selection of papers for review. Results: The initial search yielded 468 papers. After detailed evaluation, 17 papers were finally selected. Five types of studies emerged: workup of patients with symptoms and biomarker findings suggestive of NET, but with negative conventional imaging (3 papers, yield was only 13%); sensitivity (12 papers; sensitivity, 92%) and specificity (7 papers; specificity, 82%); identification of site of unknown primary in patients with metastatic NET (4 papers, yield was 44%); impact on subsequent NET patient management (4 papers, change in management in 51%); and comparison with 111In-octreotide (2 papers, sensitivity of DOTATOC on a per-lesion basis was 100%, for 111In-octreotide it was 78.2%; specificity was not available). Safety was not explicitly addressed in any study, but there were no reports of adverse events. Conclusion:68Ga-DOTATOC is useful for evaluating the presence and extent in disease for staging and restaging and for assisting in treatment decision making for patients with NET. It is also effective in locating the site of an unknown primary in NET patients who present with metastatic NET, but no known primary tumor. It also appears to be more accurate than 111In-octreotide. Although 68Ga-DOTATOC would seem to be useful in evaluating patients with suggestive symptoms and biomarker findings, it does not perform well in this setting and has low yield. Overall, it appears to be an excellent imaging agent to assess patients with known NET and frequently leads to a change in management.

Project description:IntroductionThe yield per elution of a 68Ge/68Ga generator decreases during its lifespan. This affects the number of patients injected per elution or the injected dose per patient, thereby negatively affecting the cost of examinations and the quality of PET images due to increased image noise. We aimed to investigate whether AI-based PET denoising can offset this decrease in image quality parameters.MethodsAll patients addressed to our PET unit for a 68Ga-DOTATOC PET/CT from April 2020 to February 2021 were enrolled. Forty-four patients underwent their PET scans according to Protocol_FixedDose (150 MBq) and 32 according to Protocol_WeightDose (1.5 MBq/kg). Protocol_WeightDose examinations were processed using the Subtle PET software (Protocol_WeightDoseAI). Liver and vascular SUV mean were recorded as well as SUVmax, SUVmean and metabolic tumour volume (MTV) of the most intense tumoural lesion and its background SUVmean. Liver and vascular coefficients of variation (CV), tumour-to-background and tumour-to-liver ratios were calculated.ResultsThe mean injected dose of 2.1 (0.4) MBq/kg per patient was significantly higher in the Protocol_FixedDose group as compared to 1.5 (0.1) MBq/kg for the Protocol_WeightDose group. Protocol_WeightDose led to noisier images than Protocol_FixedDose with higher CVs for liver (15.57% ± 4.32 vs. 13.04% ± 3.51, p = 0.018) and blood-pool (28.67% ± 8.65 vs. 22.25% ± 10.37, p = 0.0003). Protocol_WeightDoseAI led to less noisy images than Protocol_WeightDose with lower liver CVs (11.42% ± 3.05 vs. 15.57% ± 4.32, p < 0.0001) and vascular CVs (16.62% ± 6.40 vs. 28.67% ± 8.65, p < 0.0001). Tumour-to-background and tumour-to-liver ratios were lower for protocol_WeightDoseAI: 6.78 ± 3.49 vs. 7.57 ± 4.73 (p = 0.01) and 5.96 ± 5.43 vs. 6.77 ± 6.19 (p < 0.0001), respectively. MTVs were higher after denoising whereas tumour SUVmax were lower: the mean% differences in MTV and SUVmax were + 11.14% (95% CI = 4.84-17.43) and -3.92% (95% CI = -6.25 to -1.59).ConclusionThe degradation of PET image quality due to a reduction in injected dose at the end of the 68Ge/68Ga generator lifespan can be effectively counterbalanced by using AI-based PET denoising.

Project description:68Ga-DOTATOC PET/MRI combines the advantages of PET in the acquisition of metabolic-functional information with the high soft-tissue contrast of MRI. SUVs in tumors have been suggested to be a measure of somatostatin receptor expression. A challenge with receptor ligands is that the distribution volume is confined to tissues with tracer uptake, potentially limiting SUV quantification. In this study, various functional 3-dimensional SUV apparent diffusion coefficient (ADC) parameters and arterial tumor enhancement were tested for ability to characterize gastroenteropancreatic (GEP) neuroendocrine tumors (NETs). Methods: For this single-center, cross-sectional study, 22 patients with 24 histologically confirmed GEP NET lesions (15 men and 7 women; median age, 61 y; range, 43-81 y) who underwent hybrid 68Ga-DOTA PET/MRI at 3 T between January 2017 and July 2019 met the eligibility criteria. SUV, tumor-to-background ratio, total functional tumor volume, and mean and minimum ADC were measured on the basis of volumes of interest and examined with receiver-operating-characteristic analysis to determine cutoffs for differentiation between low- and intermediate-grade GEP NETs. The Spearman rank correlation coefficient was used to assess correlations between functional imaging parameters. Results: The ratio of PET-derived SUVmean and diffusion-weighted imaging-derived minimum ADC was introduced as a combined variable to predict tumor grade, outperforming single predictors. On the basis of a threshold ratio of 0.03, tumors could be classified as grade 2 with a sensitivity of 86% and a specificity of 100%. SUV and functional ADCs, as well as arterial contrast enhancement parameters, showed nonsignificant and mostly negligible correlations. Conclusion: Because receptor density and tumor cellularity appear to be independent, potentially complementary phenomena, the combined ratio of PET/MRI and SUVmean/ADCmin may be used as a novel biomarker allowing differentiation between grade 1 and grade 2 GEP NETs.

Dataset Information

(68)Ga-DOTATOC PET and gene expression profile in patients with neuroendocrine carcinomas: strong correlation between PET tracer uptake and gene expression of somatostatin receptor subtype 2.

Publications

(68)Ga-DOTATOC PET and gene expression profile in patients with neuroendocrine carcinomas: strong correlation between PET tracer uptake and gene expression of somatostatin receptor subtype 2.

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