Positron Emission Tomography in Breast Cancer

Conejero, J.L. Vercher; Pelegrí-Martinez, Laura; López-Aznar, D; Cózar-Santiago, M. del Puig

doi:10.3390/diagnostics5010061

Cited by 43 publications

(27 citation statements)

References 86 publications

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“…CONCLUSION We demonstrated the advantage of radiolabeled SSTR antagonists over agonists for BC targeting in a preclinical setting, shedding new light on SSTR-mediated BC imaging. The application of SSTR antagonists, combined with recent developments such as dedicated breast cameras (22) and PET radionuclides (23), is promising and may increase the importance of SSTR-mediated imaging and treatment of BC patients.…”

Section: Discussionmentioning

confidence: 99%

SSTR-Mediated Imaging in Breast Cancer: Is There a Role for Radiolabeled Somatostatin Receptor Antagonists?

et al. 2017

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Recent studies have shown enhanced tumor targeting by novel somatostatin receptor (SSTR) antagonists compared with clinically widely used agonists. However, these results have been obtained mostly in neuroendocrine tumors, and only limited data are available for cancer types with lower SSTR expression, including breast cancer (BC). To date, two studies have reported higher binding of the antagonist than the agonist in BC, but in both studies only a limited number of cases were evaluated. In this preclinical study, we further investigated whether the application of an SSTR antagonist can improve SSTR-mediated BC imaging in a large panel of BC specimens. We also generated an in vivo BC mouse model and performed SPECT/MRI and biodistribution studies. Binding ofIn-DOTA-Tyr-octreotate (SSTR agonist) and In-DOTA-JR11 (SSTR antagonist) to 40 human BC specimens was compared using in vitro autoradiography. SSTR2 immunostaining was performed to confirm SSTR2 expression of the tumor cells. Furthermore, binding of the radiolabeled SSTR agonist and antagonist was analyzed in tissue material from 6 patient-derived xenografts. One patient-derived xenograft, the estrogen receptor-positive model T126, was chosen to generate in vivo mouse models containing orthotopic breast tumors for in vivo SPECT/MRI and biodistribution studies after injection withLu-DOTA-Tyr-octreotate or Lu-DOTA-JR11.In-DOTA-JR11 binding to human BC tissue was significantly higher than In-DOTA-Tyr-octreotate binding ( < 0.001). The median ratio of antagonist binding versus agonist binding was 3.39 (interquartile range, 2-5). SSTR2 immunostaining confirmed SSTR2 expression on the tumor cells. SPECT/MRI of the mouse model found better tumor visualization with the antagonist. This result was in line with the significantly higher tumor uptake of the radiolabeled antagonist than of the agonist as measured in biodistribution studies 285 min after radiotracer injection (percentage injected dose per gram of tissue: 1.92 ± 0.43 vs. 0.90 ± 0.17; = 0.002). SSTR antagonists are promising candidates for BC imaging.

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Section: Discussionmentioning

confidence: 99%

SSTR-Mediated Imaging in Breast Cancer: Is There a Role for Radiolabeled Somatostatin Receptor Antagonists?

et al. 2017

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“…Radiotracer-based imaging approaches, such as single-photon emission computed tomography (SPECT) might provide a non-invasive in vivo assessment providing information about tumor localization and progression [23,26]. The use of radionuclides combined with molecules or existing pharmaceutical compounds, such as antitumor drugs, which preferentially accumulate in tumor tissue, has significant importance since they might enable an early and more accurate diagnosis [1–3]. …”

Section: Discussionmentioning

confidence: 99%

Technetium-99 m radiolabeled paclitaxel as an imaging probe for breast cancer in vivo

Monteiro

Fernandes

Castro

et al. 2017

Biomedicine & Pharmacotherapy

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The high incidence and mortality of breast cancer supports efforts to develop innovative imaging probes to effectively diagnose, evaluate the extent of the tumor, and predict the efficacy of tumor treatments while concurrently and selectively delivering anticancer agents to the cancer tissue. In the present study we described the preparation of technetium–99 m (99mTc)-labeled paclitaxel (PTX) and evaluated its feasibility as a radiotracer for breast tumors (4T1) in BALB/c mice. Thin Layer Chromatography (TLC) was used to determine the radiochemical purity and in vitro stability of 99mTc-PTX. PTX micelles showed a unimodal distribution with mean diameter of 13.46 ± 0.06 nm. High radiochemical purity (95.8 ± 0.3%) and in vitro stability (over than 95%), up to 24 h, were observed. Blood circulation time of 99mTc-PTX was determined in healthy BALB/c mice. 99mTc-PTX decays in a one-phase manner with a half-life of 464.3 minutes. Scintigraphic images and biodistribution were evaluated at 4, 8 and 24 h after administration of 99mTc-PTX in 4T1 tumor-bearing mice. The data showed a significant uptake in the liver, spleen and kidneys, due to the importance of these routes for excretion. Moreover, high tumor uptake was achieved, indicated by high tumor-to-muscle ratios. These findings indicate the usefulness of 99mTc-PTX as a radiotracer to identify 4T1 tumor in animal models. In addition, 99mTc-PTX might be used to follow-up treatment protocols in research, being able to provide information about tumor progression after therapy.

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“…Also, dedicated breast PET cameras can be used. These dedicated cameras have improved sensitivity and specificity compared to whole body PET, because of a restricted field of view, resulting in higher cancer detection [22]. Furthermore, tumors can be treated with therapeutic radioligands.…”

Section: Discussionmentioning

confidence: 99%

Prospects of Targeting the Gastrin Releasing Peptide Receptor and Somatostatin Receptor 2 for Nuclear Imaging and Therapy in Metastatic Breast Cancer

et al. 2017

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BackgroundThe gastrin releasing peptide receptor (GRPR) and the somatostatin receptor 2 (SSTR2) are overexpressed on primary breast cancer (BC), making them ideal candidates for receptor-mediated nuclear imaging and therapy. The aim of this study was to determine whether these receptors are also suitable targets for metastatic BC.MethodsmRNA expression of human BC samples were studied by in vitro autoradiography and associated with radioligand binding. Next, GRPR and SSTR2 mRNA levels of 60 paired primary BCs and metastases from different sites were measured by quantitative reverse transcriptase polymerase chain reaction. Receptor mRNA expression levels were associated with clinico-pathological factors and expression levels of primary tumors and corresponding metastases were compared.ResultsBinding of GRPR and SSTR radioligands to tumor tissue correlated significantly with receptor mRNA expression. High GRPR and SSTR2 mRNA levels were associated with estrogen receptor (ESR1)-positive tumors (p<0.001 for both receptors). There was no significant difference in GRPR mRNA expression of primary tumors versus paired metastases. Regarding SSTR2 mRNA expression, there was also no significant difference in the majority of cases, apart from liver and ovarian metastases which showed a significantly lower expression compared to the corresponding primary tumors (p = 0.02 and p = 0.03, respectively).ConclusionTargeting the GRPR and SSTR2 for nuclear imaging and/or treatment has the potential to improve BC care in primary as well as metastatic disease.

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Positron Emission Tomography in Breast Cancer

Cited by 43 publications

References 86 publications

SSTR-Mediated Imaging in Breast Cancer: Is There a Role for Radiolabeled Somatostatin Receptor Antagonists?

SSTR-Mediated Imaging in Breast Cancer: Is There a Role for Radiolabeled Somatostatin Receptor Antagonists?

Technetium-99 m radiolabeled paclitaxel as an imaging probe for breast cancer in vivo

Prospects of Targeting the Gastrin Releasing Peptide Receptor and Somatostatin Receptor 2 for Nuclear Imaging and Therapy in Metastatic Breast Cancer

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