Prevalence and Clinical Correlations of Somatostatin Receptor-2 (SSTR2) Expression in Neuroblastoma

Alexander, Natasha; Marrano, Paula; Thorner, Paul; Naranjo, Arlene; Ryn, Collin Van; Martı́nez, Daniel; Batra, Vandana; Zhang, Libo; Irwin, Meredith S.; Baruchel, Sylvain

doi:10.1097/mph.0000000000001326

Cited by 19 publications

(26 citation statements)

References 40 publications

(71 reference statements)

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“…Somatostatin receptor 2 (SSTR2) is expressed by many tumor types including the majority of NB tumors, with expression in clinical samples ranging from 77 to 100% depending on the method of detection [8][9][10][11][12], and there is a negative correlation between SSTR2 expression and clinical risk [10]. SSTR2 is, therefore, considered to be an important target for the development of somatostatin analogues for molecular imaging and radionuclide therapy [13].…”

Section: Introductionmentioning

confidence: 99%

Detection and therapy of neuroblastoma minimal residual disease using [64/67Cu]Cu-SARTATE in a preclinical model of hepatic metastases

Dearling

Dam²,

Harris³

et al. 2021

EJNMMI Res

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Background A major challenge to the long-term success of neuroblastoma therapy is widespread metastases that survive initial therapy as minimal residual disease (MRD). The SSTR2 receptor is expressed by most neuroblastoma tumors making it an attractive target for molecularly targeted radionuclide therapy. SARTATE consists of octreotate, which targets the SSTR2 receptor, conjugated to MeCOSar, a bifunctional chelator with high affinity for copper. Cu-SARTATE offers the potential to both detect and treat neuroblastoma MRD by using [64Cu]Cu-SARTATE to detect and monitor the disease and [67Cu]Cu-SARTATE as the companion therapeutic agent. In the present study, we tested this theranostic pair in a preclinical model of neuroblastoma MRD. An intrahepatic model of metastatic neuroblastoma was established using IMR32 cells in nude mice. The biodistribution of [64Cu]Cu-SARTATE was measured using small-animal PET and ex vivo tissue analysis. Survival studies were carried out using the same model: mice (6–8 mice/group) were given single doses of saline, or 9.25 MBq (250 µCi), or 18.5 MBq (500 µCi) of [67Cu]Cu-SARTATE at either 2 or 4 weeks after tumor cell inoculation. Results PET imaging and ex vivo biodistribution confirmed tumor uptake of [64Cu]Cu-SARTATE and rapid clearance from other tissues. The major clearance tissues were the kidneys (15.6 ± 5.8% IA/g at 24 h post-injection, 11.5 ± 2.8% IA/g at 48 h, n = 3/4). Autoradiography and histological analysis confirmed [64Cu]Cu-SARTATE uptake in viable, SSTR2-positive tumor regions with mean tumor uptakes of 14.1–25.0% IA/g at 24 h. [67Cu]Cu-SARTATE therapy was effective when started 2 weeks after tumor cell inoculation, extending survival by an average of 13 days (30%) compared with the untreated group (mean survival of control group 43.0 ± 8.1 days vs. 55.6 ± 9.1 days for the treated group; p = 0.012). No significant therapeutic effect was observed when [67Cu]Cu-SARTATE was started 4 weeks after tumor cell inoculation, when the tumors would have been larger (control group 14.6 ± 8.5 days; 9.25 MBq group 9.5 ± 1.6 days; 18.5 MBq group 15.6 ± 4.1 days; p = 0.064). Conclusions Clinical experiences of peptide-receptor radionuclide therapy for metastatic disease have been encouraging. This study demonstrates the potential for a theranostic approach using [64/67Cu]Cu-SARTATE for the detection and treatment of SSTR2-positive neuroblastoma MRD.

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Section: Introductionmentioning

confidence: 99%

Detection and therapy of neuroblastoma minimal residual disease using [64/67Cu]Cu-SARTATE in a preclinical model of hepatic metastases

Dearling

Dam²,

Harris³

et al. 2021

EJNMMI Res

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“…This has been described by several cases of neuroblastoma patients [ 79 , 88 , 89 ]. On the other hand, [ 68 Ga]Ga-DOTA peptide imaging may be negative in tumors with low SSTR expression, more likely seen in poorly differentiated tumors [ 90 ].…”

Section: [ 68 Ga]ga-dota Peptidesmentioning

confidence: 99%

“…Nevertheless, higher SSTR2 expression is correlated with higher [ 68 Ga]Ga-DOTATATE uptake [ 94 ]. Several studies found that higher SSTR2 expression is strongly associated with non-high-risk and differentiated neuroblastoma, and lack of SSTR expression has been found to correlate with advanced disease and decreased survival [ 82 , 90 , 95 , 96 , 97 ], while others did not find any prognostic relation [ 37 ].…”

Section: [ 68 Ga]ga-dota Peptidesmentioning

confidence: 99%

Nuclear Medicine Imaging in Neuroblastoma: Current Status and New Developments

Samim

Tytgat

Bleeker³

et al. 2021

JPM

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Neuroblastoma is the most common extracranial solid malignancy in children. At diagnosis, approximately 50% of patients present with metastatic disease. These patients are at high risk for refractory or recurrent disease, which conveys a very poor prognosis. During the past decades, nuclear medicine has been essential for the staging and response assessment of neuroblastoma. Currently, the standard nuclear imaging technique is meta-[123I]iodobenzylguanidine ([123I]mIBG) whole-body scintigraphy, usually combined with single-photon emission computed tomography with computed tomography (SPECT-CT). Nevertheless, 10% of neuroblastomas are mIBG non-avid and [123I]mIBG imaging has relatively low spatial resolution, resulting in limited sensitivity for smaller lesions. More accurate methods to assess full disease extent are needed in order to optimize treatment strategies. Advances in nuclear medicine have led to the introduction of radiotracers compatible for positron emission tomography (PET) imaging in neuroblastoma, such as [124I]mIBG, [18F]mFBG, [18F]FDG, [68Ga]Ga-DOTA peptides, [18F]F-DOPA, and [11C]mHED. PET has multiple advantages over SPECT, including a superior resolution and whole-body tomographic range. This article reviews the use, characteristics, diagnostic accuracy, advantages, and limitations of current and new tracers for nuclear medicine imaging in neuroblastoma.

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“…It is involved in secretion, proliferation, and the induction of apoptosis (35). For pediatric cancers, SSTR-2A expression was reported for neuroblastoma tumors by Alexander et al as well as for neuro-oncological malignancies (e.g., glioblastomas and medulloblastomas) (36)(37)(38). Analogs of somatostatin, the natural ligand of SSTR-2A, have successfully been developed to inhibit neuroendocrine tumor growth.…”

Section: From Adult Oncology To Pediatric Oncologymentioning

confidence: 99%

The Current Status and Future Potential of Theranostics to Diagnose and Treat Childhood Cancer

2020

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In theranostics (i.e., therapy and diagnostics) radiopharmaceuticals are used for both therapeutic and diagnostic purposes by targeting one specific tumor receptor. Biologically relevant compounds, e.g., receptor ligands or drugs, are labeled with radionuclides to form radiopharmaceuticals. The possible applications are multifold: visualization of biological processes or tumor biology in vivo, diagnosis and tumor staging, therapy planning, and treatment of specific tumors. Theranostics research is multidisciplinary and allows for the rapid translation of potential tumor targets from preclinical research to "firstin-man" clinical studies. In the last decade, the use of theranostics has seen an unprecedented value for adult cancer patients. Several radiopharmaceuticals are routinely used in clinical practice (e.g., [ 68 Ga/ 177 Lu]DOTATATE), and dozens are under (pre)clinical development. In contrast to these successes in adult oncology, theranostics have scarcely been developed to diagnose and treat pediatric cancers. To date, [ 123/131 I] meta-iodobenzylguanidine ([ 123/131 I]mIBG) is the only available and approved theranostic in pediatric oncology. mIBG targets the norepinephrine transporter, expressed by neuroblastoma tumors. For most pediatric tumors, including neuroblastoma, there is a clear need for novel and improved radiopharmaceuticals for imaging and therapy. The strategy of theranostics for pediatric oncology can be divided in (1) the improvement of existing theranostics, (2) the translation of theranostics developed in adult oncology for pediatric purposes, and (3) the development of novel theranostics for pediatric tumorspecific targets. Here, we describe the recent advances in theranostics development in pediatric oncology and shed a light on how this methodology can affect diagnosis and provide additional treatment options for these patients.

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Prevalence and Clinical Correlations of Somatostatin Receptor-2 (SSTR2) Expression in Neuroblastoma

Cited by 19 publications

References 40 publications

Detection and therapy of neuroblastoma minimal residual disease using [64/67Cu]Cu-SARTATE in a preclinical model of hepatic metastases

Detection and therapy of neuroblastoma minimal residual disease using [64/67Cu]Cu-SARTATE in a preclinical model of hepatic metastases

Nuclear Medicine Imaging in Neuroblastoma: Current Status and New Developments

The Current Status and Future Potential of Theranostics to Diagnose and Treat Childhood Cancer

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