Molecular imaging with 68Ga-SSTR PET/CT and correlation to immunohistochemistry of somatostatin receptors in neuroendocrine tumours

Kaemmerer, Daniel; Peter, Luisa; Lupp, Amelie; Schulz, Stefan; Sänger, Jörg; Prasad, Vikas; Kulkarni, Harshad; Haugvik, Sven-Petter; Hommann, Merten; Baüm, Richard

doi:10.1007/s00259-011-1846-5

Cited by 134 publications

(92 citation statements)

References 24 publications

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“…Indeed, 76.5% of MCCs of our series expressed at least one SSTR, which is in line with the proportion of tumours accurately detected by SRI [19,20,21]. Results from SRI are related to the SSTR expression on the immunohistochemistry of well-differentiated extracutaneous NETs [14,55,56,57]. In our cohort, patients had not been evaluated with SRI, so we could not evaluate the relationship between SSTR expression and SRI results.…”

Section: Discussionsupporting

confidence: 57%

Somatostatin Receptors 2A and 5 Are Expressed in Merkel Cell Carcinoma with No Association with Disease Severity

Gardair¹,

Samimi

Touzé

et al. 2015

Neuroendocrinology

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Background/Aims: Merkel cell carcinoma (MCC) is a rare high-grade neuroendocrine tumour of the skin. It has been speculated that MCCs express somatostatin receptors (SSTRs), but this has never been assessed in a large series of MCCs. The main aim of this study was to assess the expression of SSTR2A and SSTR5 in MCC tumours. The secondary aims were to assess whether expression of SSTR was associated with the Ki67 proliferative index, Merkel cell polyomavirus (MCPyV) status, clinical characteristics and outcome. Methods: Clinical data and tumours were collected from an ongoing cohort of French patients with MCC. Immunohistochemistry was performed with anti-SSTR2A and anti-SSTR5 monoclonal antibodies, and tumours were classified into 3 groups: ‘no expression', ‘low expression' and ‘moderate expression' using an SSTR staining score. Results: SSTR expression was assessed for 105 MCC tissue samples from 98 patients, and clinical characteristics were available for 87 of them. SSTR expression was consistent between the primary skin tumour and the corresponding metastases for SSTR2A and SSTR5 in 3/7 and 6/7 cases, respectively. SSTR2A and SSTR5 were expressed in 58 cases (59.2%) and in 44 cases (44.9%), respectively. Overall, at least one SSTR was expressed in 75 tumours (76.5%). SSTR expression was not associated with clinical characteristics, Ki67 proliferative index, recurrence-free survival or MCC-specific survival. Expression of SSTR2A was associated with MCPyV status in MCC tumours but not SSTR5. Conclusion: SSTRs were expressed in a high proportion of MCCs, although expression was heterogeneous between tumours and was not associated with disease severity.

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Section: Discussionsupporting

confidence: 57%

Somatostatin Receptors 2A and 5 Are Expressed in Merkel Cell Carcinoma with No Association with Disease Severity

Gardair¹,

Samimi

Touzé

et al. 2015

Neuroendocrinology

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“…Also the high prevalence of sst 3 in pheochromocytoma and neuroendocrine tumors found in our investigations with UMB-5 corresponds well to earlier data obtained with polyclonal antibodies [4,21,27,41]. In contrast to these previous investigations showing primarily cytoplasmic immunoreactivity, the present study revealed a predominance of plasma membrane staining.…”

Section: Discussioncontrasting

confidence: 56%

Reassessment of sst<sub>3</sub> Somatostatin Receptor Expression in Human Normal and Neoplastic Tissues Using the Novel Rabbit Monoclonal Antibody UMB-5

Lupp

Nagel²,

Doll³

et al. 2012

Neuroendocrinology

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Background: Among the five somatostatin receptors (sst₁-sst₅), the sst₃ receptor displays a distinct pharmacological profile. Like sst₂, the sst₃ receptor efficiently internalizes radiolabeled somatostatin analogs. Unlike sst₂, however, internalized sst₃ receptors are rapidly transferred to lysosomes for degradation. Apart from this, very little is known about the clinical relevance of the sst₃ receptor, which may in part be due to the lack of specific monoclonal sst₃ antibodies. Methods: Here, we have extensively characterized the novel rabbit monoclonal anti-human sst₃ antibody UMB-5 using transfected cells and receptor-expressing tissues. UMB-5 was then subjected to immunohistochemical staining of a series of 190 formalin-fixed, paraffin-embedded normal and neoplastic human tissues. Results: Specificity of UMB-5 was demonstrated by detection of a broad band migrating at a molecular weight of 70,000–85,000 in immunoblots from human pituitary. After enzymatic deglycosylation, the size of this band decreased to a molecular weight of 45,000. Tissue immunostaining was completely abolished by pre-adsorption of UMB-5 with its immunizing peptide. In addition, UMB-5 detected distinct cell populations in human tissues like pancreatic islands, anterior pituitary, adrenal cortex, adrenal medulla, and enteric ganglia, similar to that seen with a rabbit polyclonal antibody generated against a different carboxyl-terminal epitope of the sst₃ receptor. In a comparative immunohistochemical study, UMB-5 yielded predominant plasma membrane staining in the majority of pituitary adenomas, pheochromocytomas, and a subset of neuroendocrine tumors. The sst₃ receptor was also present in many glioblastomas, pancreatic, breast, cervix, and ovarian carcinomas. Conclusion: The rabbit monoclonal antibody UMB-5 may prove of great value in the identification of sst₃-expressing tumors during routine histopathological examinations. Given its unique trafficking properties, these tumors may be potential candidates for sst₃-directed receptor radiotherapy.

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“…Two papers reported how the 68 Ga-DOTANOC SUV max correlates with somatostatin receptor expression (9,23), and two investigated the potential prognostic role of SUV max in patients with neuroendocrine tumors with different primary sites (9,10). However, pNETs generally show more aggressive clinical behavior than other forms of NET (8,11), with 5-y survival rates ranging between 25% and 75% (2,24,25).…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of ⁶⁸Ga-DOTANOC PET/CT SUV_max in Patients with Neuroendocrine Tumors of the Pancreas

et al. 2015

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This study was performed to investigate the role of 68 Ga-DOTANOC SUV max as a potential prognostic factor in patients with pancreatic neuroendocrine tumor (pNET). Methods: Among the patients who underwent 68 Ga-DOTANOC PET/CT, we retrospectively collected the data of those who had G1 or G2 pNET (2010 World Health Organization classification), presented with disease on PET/CT and CT, and had at least 6 mo of follow-up. Patients with multiple endocrine neoplasia were excluded. Results: Overall, 43 patients were included. No significant differences in SUV max were observed with respect to sex, tumor syndrome, stage, World Health Organization classification, or Ki-67. During follow-up (median, 20 mo), 11 patients (35.6%; median, 33 mo; interquartile range, 20-48 mo) had stable disease and 32 (74.4%; median, 19 mo; interquartile range, 14-26 mo) had progressive disease. SUV max at 24 mo of follow-up was significantly higher (P 5 0.022) in patients with stable disease than in patients with progressive disease. The best SUV max cutoff ranged from 37.8 to 38.0. The major risk factors for progression included an SUV max of no more than 37.8 (hazard ratio, 3.09; P 5 0.003), a Ki-67 of more than 5% (hazard ratio, 2.89; P 5 0.009), and medical therapy alone (hazard ratio, 2.36; P 5 0.018). Advanced stage (IV) (P 5 0.026), an SUV max of less than 37.8 (P 5 0.043), and medical therapy alone (P 5 0.015) were also confirmed at multivariate analysis. Median progression-free survival was 23 mo. Significant differences in progression-free survival were observed in relationship to Ki-67 (median, 45 mo for Ki-67 # 5% and 20 mo for Ki-67 . 5%; P 5 0.005), SUV max (,37.8 vs. .38.0: 16.0 vs. 27.0 mo; P 5 0.002), and type of therapy (medical vs. peptide receptor radionuclide therapy: 16.0 vs. 26.0 mo; P 5 0.014). Conclusion: 68 Ga-DOTANOC SUV max is a relevant prognostic factor in patients with G1 and G2 pNET, and its routine use will improve disease characterization and management in these patients, who may present with atypical cases showing heterogeneous clinical behavior.

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Molecular imaging with 68Ga-SSTR PET/CT and correlation to immunohistochemistry of somatostatin receptors in neuroendocrine tumours

Cited by 134 publications

References 24 publications

Somatostatin Receptors 2A and 5 Are Expressed in Merkel Cell Carcinoma with No Association with Disease Severity

Somatostatin Receptors 2A and 5 Are Expressed in Merkel Cell Carcinoma with No Association with Disease Severity

Reassessment of sst<sub>3</sub> Somatostatin Receptor Expression in Human Normal and Neoplastic Tissues Using the Novel Rabbit Monoclonal Antibody UMB-5

Prognostic Value of ⁶⁸Ga-DOTANOC PET/CT SUV_max in Patients with Neuroendocrine Tumors of the Pancreas

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Molecular imaging with 68Ga-SSTR PET/CT and correlation to immunohistochemistry of somatostatin receptors in neuroendocrine tumours

Cited by 134 publications

References 24 publications

Somatostatin Receptors 2A and 5 Are Expressed in Merkel Cell Carcinoma with No Association with Disease Severity

Somatostatin Receptors 2A and 5 Are Expressed in Merkel Cell Carcinoma with No Association with Disease Severity

Reassessment of sst<sub>3</sub> Somatostatin Receptor Expression in Human Normal and Neoplastic Tissues Using the Novel Rabbit Monoclonal Antibody UMB-5

Prognostic Value of 68Ga-DOTANOC PET/CT SUVmax in Patients with Neuroendocrine Tumors of the Pancreas

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Prognostic Value of ⁶⁸Ga-DOTANOC PET/CT SUV_max in Patients with Neuroendocrine Tumors of the Pancreas