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Research ArticleTheranostics

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

Simone U. Dalm, Joost Haeck, Gabriela N. Doeswijk, Erik de Blois, Marion de Jong and Carolien H.M. van Deurzen
Journal of Nuclear Medicine October 2017, 58 (10) 1609-1614; DOI: https://doi.org/10.2967/jnumed.116.189035
Simone U. Dalm
1Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands; and
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Joost Haeck
1Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands; and
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Gabriela N. Doeswijk
1Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands; and
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Erik de Blois
1Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands; and
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Marion de Jong
1Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands; and
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Carolien H.M. van Deurzen
2Department of Pathology, Erasmus MC, Rotterdam, The Netherlands
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  • FIGURE 1.
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    FIGURE 1.

    (A) Representative autoradiography results for 111In-DOTA-JR11 and 111In-DOTA-Tyr3-octreotate. Hematoxylin and eosin (H&E) staining and SSTR2 immunohistochemistry (IHC) staining were performed on adjacent tissue sections to indicate tumor cells and SSTR2 expression, respectively. (B) Quantified uptake (net %AD, corrected for unspecific binding) of radiotracers. (C) Ratio of radiotracer binding (antagonist to agonist).

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    FIGURE 2.

    (A) Autoradiography results (without and with excess of unlabeled octreotide to determine specificity of binding) of tumor material from 6 patient-derived xenografts. Scaling was similar for agonist and antagonist binding to same patient-derived xenograft but not to different patient-derived xenografts. Therefore, uptake between different patient-derived xenografts cannot be compared on the basis of the images. Tumor sections with low radioligand binding (blocked tumor section of patient-derived xenograft T283 and T201) are color-corrected to enable visualization and may not correctly correlate with quantified uptake in B. (B) Quantified uptake (total %AD and net %AD corrected for unspecific binding) of 111In-DOTA-JR11 and 111In-DOTA-Tyr3-octreotate for autoradiography in A, with ER, PR, and HER2 status of patient-derived xenograft models.

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    FIGURE 3.

    (A and B) SPECT/MR images and quantified tumor uptake after injection of 177Lu-DOTA-JR11 (A) and 177Lu-DOTA-Tyr3-octreotate (B). Scales are equal for all images. Dotted lines indicate area scanned with SPECT. Arrows indicate tumor xenografts. (C and D) Hematoxylin and eosin staining (C) and SSTR2 immunostaining (D) of excised tumors showing SSTR2 expression. Arrows indicate normal tissue (epithelial lining of duct) without SSTR2 expression.

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    FIGURE 4.

    Radioactivity uptake and tumor-to-organ ratios in excised tumors and organs after imaging studies. Blocking studies were performed by injection of radiotracers plus excess of unlabeled peptide analogs. Ad = adrenals; Bl = blood; GI = gastrointestinal tract; Ki = kidney; Li = liver; Mu = muscle; Pa = pancreas; Tu = tumor.

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    TABLE 1

    SSTR Affinity of DOTA-JR11 and DOTA-Tyr3-Octreotate

    RadioligandSSTR1SSTR2SSTR3SSTR4SSTR5
    DOTA-JR11*>1,0000.72 ± 0.12>1,000>1,000>1,000
    DOTA-Tyr3-octreotate†>10,0001.5 ± 0.4>1,000453 ± 176547 ± 160
    • ↵* Data are from Fani et al. (14).

    • ↵† Data are from Reubi et al. (15).

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    TABLE 2

    Results of SSTR2 Immunostaining

    FindingWeakModerateStrongTotal
    Heterogeneous16%8%5%30%
    Homogenous35%8%27%70%
    Total51%16%32%100%
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Journal of Nuclear Medicine: 58 (10)
Journal of Nuclear Medicine
Vol. 58, Issue 10
October 1, 2017
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SSTR-Mediated Imaging in Breast Cancer: Is There a Role for Radiolabeled Somatostatin Receptor Antagonists?
Simone U. Dalm, Joost Haeck, Gabriela N. Doeswijk, Erik de Blois, Marion de Jong, Carolien H.M. van Deurzen
Journal of Nuclear Medicine Oct 2017, 58 (10) 1609-1614; DOI: 10.2967/jnumed.116.189035

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SSTR-Mediated Imaging in Breast Cancer: Is There a Role for Radiolabeled Somatostatin Receptor Antagonists?
Simone U. Dalm, Joost Haeck, Gabriela N. Doeswijk, Erik de Blois, Marion de Jong, Carolien H.M. van Deurzen
Journal of Nuclear Medicine Oct 2017, 58 (10) 1609-1614; DOI: 10.2967/jnumed.116.189035
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Keywords

  • breast cancer
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  • somatostatin receptor
  • agonist
  • antagonist
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