The role of technetium-99m-labeled octreotide acetate scintigraphy in suspected breast cancer and correlates with expression of SSTR

Wang, Feng; Wang, Zizheng; Wu, Jie; Qu, Wei; Yao, Weixuan; Zhao, Jinmin; Zi-jun, Liu

doi:10.1016/j.nucmedbio.2008.04.010

Cited by 14 publications

(6 citation statements)

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“…Compared to NETs, breast cancer sstr2 density is lower and more heterogeneous as determined using autoradiography (Reubi et al 2002 ; Cescato et al 2011 ) and PET/CT imaging (Elgeti et al 2008 ). Diagnostic SPECT and scintigraphy with 111 In-pentatreotide and 99m Tc-depreotide, have been explored clinically in patients with sstr2-positive breast cancer (Alberini et al 2000 ; van Eijck et al 1994 ; Wang et al 2008 ). Sensitivity suffered in these initial studies, partly due to the low resolution of conventional scintigraphy, as well as the lower and more heterogeneous expression of sstr2 on breast carcinoma compared to NETs (Alberini et al 2000 ; van Eijck et al 1994 ; Wang et al 2008 ).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of agonist and antagonist radioligands for somatostatin receptor imaging of breast cancer using positron emission tomography

Dude

Zhang

Rousseau

et al. 2017

EJNMMI radiopharm. chem.

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BackgroundThe somatostatin receptor subtype 2 (sstr2) is expressed on a majority of luminal breast cancers, however SPECT and scintigraphy imaging with agonistic sstr2 probes has been sub-optimal. High affinity antagonists can access more binding sites on the cell surface, resulting in higher tumor uptake and improved sensitivity. We compared the tumor uptake and biodistribution of the antagonist 68Ga-NODAGA-JR11 with two agonists 68Ga-DOTA-Tyr3-octreotide (68Ga-DOTATOC) and 68Ga-DOTA-Tyr3-octreotate (68Ga-DOTATATE), in the human, sstr2-positive, luminal breast cancer model: ZR-75-1.ResultsPeptides were assayed for binding affinity using a filtration-based competitive assay to sstr2. natGa-DOTATOC and natGa-DOTATATE had excellent affinity (inhibition constant Ki: 0.9 ± 0.1 nM and 1.4 ± 0.3 nM respectively) compared to natGa-NODAGA-JR11 (25.9 ± 0.2 nM). The number of binding sites on ZR-75-1 cells was determined in vitro by saturation assays. Agonist 67/natGa-DOTATOC bound to 6.64 ± 0.39 × 104 sites/cells, which was 1.5-fold higher than 67/natGa-NODAGA-JR11 and 2.3-fold higher than 67/natGa-DOTATATE. All three 68Ga-labeled peptides were obtained in good decay-corrected radiochemical yield (61-68%) and were purified by high performance liquid chromatography to ensure high specific activity (137 – 281 MBq/nmol at the end of synthesis). NOD scid gamma mice bearing ZR-75-1 tumors were injected intravenously with the labeled peptides and used for PET/CT imaging and biodistribution at 1 h post-injection. We found that 68Ga-DOTATOC had the highest tumor uptake (18.4 ± 2.9%ID/g), followed by 68Ga-DOTATATE (15.2 ± 2.2%ID/g) and 68Ga-NODAGA-JR11 (12.2 ± 0.8%ID/g). Tumor-to-blood and tumor-to-muscle ratios were also higher for the agonists (>40 and >150 respectively), compared to the antagonist (15.6 ± 2.2 and 45.2 ± 11.6 respectively).ConclusionsThe antagonist 68Ga-NODAGA-JR11 had the lowest tumor uptake and contrast compared to agonists 68Ga-DOTATOC and 68Ga-DOTATATE in ZR-75-1 xenografts.The main contributing factor to this result could be the use of an endogenously expressing cell line, which may differ from previously published transfected models in the number of low-affinity, antagonist-specific binding sites. The relative merit of agonists versus antagonists for sstr2 breast cancer imaging warrants further investigation, first in preclinical models with other sstr2-positive breast cancer xenografts, and ultimately in luminal breast cancer patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s41181-017-0023-y) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Evaluation of agonist and antagonist radioligands for somatostatin receptor imaging of breast cancer using positron emission tomography

Dude

Zhang

Rousseau

et al. 2017

EJNMMI radiopharm. chem.

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“…In the preclinical study by Chereau et al [55], 68 Ga-DOTA-TOC imaging was compared to 18 F-FDG PET in a BC xenograft mouse model resulting in two times higher uptake of 68 Ga-DOTA-TOC compared to 18 F-FDG. Concerning clinical investigations, in our previous review we discussed earlier clinical studies [56,57,58,59,60,61,62,63,64,65,66] on SSTR-mediated imaging, showing very variable sensitivities and specificities ranging from 36%–100% and 22%–100%, respectively [67]. Figure 3A shows an example of SSTR-mediated imaging in BC patients.…”

Section: Somatostatin Receptor (Sstr)-mediated Bc Imagingmentioning

confidence: 99%

“…Images are adapted from studies by Wang et al [64] and Maina and Bergsma et al [80], respectively. ( A ) 99m Tc-octreotide (a SSTR-targeting radiotracer) scintigraphy identifying SSTR-positive BC tumors.…”

Section: Figurementioning

confidence: 99%

“…2008, 35 , 665–671. Copyright, with permission from Elsevier [64]; ( B ) 68 Ga-SB3 scan in a BC patient, demonstrating GRPR-positive bone metastasis in the skull: frontal bone on the left side (part II, SUV max 2.4) and bone marrow metastasis in the right proximal femur (part III, arrow, SUV max 7.8). Part I MIP; part II fused axial PET/CT image and part III fused coronal PET/CT image.…”

Section: Figurementioning

confidence: 99%

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Review: Receptor Targeted Nuclear Imaging of Breast Cancer

Dalm

Verzijlbergen

Jong

2017

IJMS

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Receptor targeted nuclear imaging directed against molecular markers overexpressed on breast cancer (BC) cells offers a sensitive and specific method for BC imaging. Currently, a few targets such as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), somatostatin receptor (SSTR), and the gastrin releasing peptide receptor (GRPR) are being investigated for this purpose. Expression of these targets is BC subtype dependent and information that can be gained from lesion visualization is dependent on the target; ER-targeting radiotracers, e.g., can be used to monitor response to anti-estrogen treatment. Here we give an overview of the studies currently under investigation for receptor targeted nuclear imaging of BC. Main findings of imaging studies are summarized and (potential) purposes of lesion visualization by targeting these molecular markers are discussed. Since BC is a very heterogeneous disease and molecular target expression can vary per subtype, but also during disease progression or under influence of treatment, radiotracers for selected imaging purposes should be chosen carefully.

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“…The discovery that SST receptors are expressed on a multitude of tumor types, including those of the breast (50-75%), coupled with the diagnostic and therapeutic success of OctreoScan ® in patients with neuroendocrine carcinomas, generated interest in the potential expansion of OctreoScan ® 's clinical use. While the successful scintigraphic detection of both primary and metastatic breast cancer has been reported with OctreoScan ® in 50 to 94% of breast cancer cases, these figures may represent an overestimation as nonspecific uptake by nonmalignant breast tissue is observed in 15% of patients (Bajc et al, 1996;Reubi, 2008;Wang et al, 2008). In addition to the nonspecific uptake observed with OctreoScan ® , the low density of SST receptors (SSTR 2A and SSTR 5 ) present in carcinomas of the breast combined with their heterogeneous expression pattern have prevented the acceptance of this agent for the routine diagnosis of breast cancer.…”

Section: Early Radiopharmaceuticalsmentioning

confidence: 99%

Molecular Imaging of Breast Cancer Tissue via Site-Directed Radiopharmaceuticals

Jackson¹,

Retzloff²,

Nanda³

et al. 2011

Breast Cancer - Recent Advances in Biology, Imaging and Therapeutics

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The role of technetium-99m-labeled octreotide acetate scintigraphy in suspected breast cancer and correlates with expression of SSTR

Cited by 14 publications

References 30 publications

Evaluation of agonist and antagonist radioligands for somatostatin receptor imaging of breast cancer using positron emission tomography

Evaluation of agonist and antagonist radioligands for somatostatin receptor imaging of breast cancer using positron emission tomography

Review: Receptor Targeted Nuclear Imaging of Breast Cancer

Molecular Imaging of Breast Cancer Tissue via Site-Directed Radiopharmaceuticals

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