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Research ArticleTheranostics

Evaluation of 111In-DOTA-5D3, a Surrogate SPECT Imaging Agent for Radioimmunotherapy of Prostate-Specific Membrane Antigen

Sangeeta Ray Banerjee, Vivek Kumar, Ala Lisok, Donika Plyku, Zora Nováková, Mary Brummet, Bryan Wharram, Cyril Barinka, Robert Hobbs and Martin G. Pomper
Journal of Nuclear Medicine March 2019, 60 (3) 400-406; DOI: https://doi.org/10.2967/jnumed.118.214403
Sangeeta Ray Banerjee
1Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland; and
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Vivek Kumar
1Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland; and
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Ala Lisok
1Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland; and
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Donika Plyku
1Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland; and
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Zora Nováková
2Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Vestec, Czech Republic
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Mary Brummet
1Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland; and
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Bryan Wharram
1Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland; and
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Cyril Barinka
2Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Vestec, Czech Republic
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Robert Hobbs
1Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland; and
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Martin G. Pomper
1Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland; and
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  • FIGURE 1.
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    FIGURE 1.

    (A) In vitro binding specificity of 111In-DOTA-5D3 in PSMA(+) PC3 PIP and PSMA(−) PC3 flu cell lines at 37°C. (B) Immunoreactive fractions of 111In-DOTA-5D3 in PSMA(+) PC3 PIP cells was determined as 1/y (x = 0). (C) Cell surface PSMA expression by flow cytometry illustrated by overlapping histograms and mean fluorescence intensity (MFI) for 4 different cell lines: CHO (Chinese hampster ovary cell line with no staining with anti-PSMA mAb), PC3 flu (human PC3 with no staining with anti-PSMA mAb), PC3 PIP (human PC3 with PSMA-positive staining with anti-PSMA mAb), and LNCaP (human prostate cell line). Notice shift for no staining (CHO, gray; flu, green) and staining with PE antihuman PSMA (FOLH1) mAb (LNCaP, blue; PIP, red). PSMA PE = phycoerythrin (PE)-conjugated anti-PSMA antibody.

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    FIGURE 2.

    (A) Tissue biodistribution of 111In-DOTA-5D3 in male NOD-SCID mice bearing PSMA(+) PC3 PIP and PSMA(−) PC3 flu tumors on either flank (n = 4). (B) Selected PSMA(+) PC3 PIP tumor-to-normal organ ratios. (C) Binding specificity assessed by blockade with coinjection of either 10- or 50-fold excess of nonradiolabeled 5D3. (D) Immunohistochemistry of PSMA expression and negative control (no PSMA staining) of frozen tissue sections of PSMA(+) PC3 PIP tumor and PSMA(−)PC3 flu tumor at ×10 magnification obtained from biodistribution experiment at 24 h after injection of 111In-DOTA-5D3 and from blocking experiment at 24 h using 50-fold excess of 5D3.

  • FIGURE 3.
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    FIGURE 3.

    Biodistribution analysis at 2 h and 24 h after injection of 111In-DOTA-5D3 in male NOD-SCID bearing PSMA(+) PC3 PIP and PSMA(−) PC3 flu tumors on either flank (n = 4) and in male CD-1 mice (n = 3).

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    FIGURE 4.

    Whole-body volume rendering SPECT/CT images in male NOD-SCID mice showing uptake of 11In-DOTA-5D3 in normal tissues (e.g., liver, kidneys) and PSMA(+) PC3 PIP and PSMA(−) PC3 flu tumors.

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    FIGURE 5.

    (A) Calculated human organ time-integrated activity coefficients. (B) Estimated human organ absorbed doses (mGy/MBq). Absorbed doses were calculated on the basis of murine biodistribution data, which were converted into adult human absorbed doses. Calculated time-integrated activities were used as input in OLINDA/EXM using adult male phantom for normal tissues.

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Journal of Nuclear Medicine: 60 (3)
Journal of Nuclear Medicine
Vol. 60, Issue 3
March 1, 2019
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Evaluation of 111In-DOTA-5D3, a Surrogate SPECT Imaging Agent for Radioimmunotherapy of Prostate-Specific Membrane Antigen
Sangeeta Ray Banerjee, Vivek Kumar, Ala Lisok, Donika Plyku, Zora Nováková, Mary Brummet, Bryan Wharram, Cyril Barinka, Robert Hobbs, Martin G. Pomper
Journal of Nuclear Medicine Mar 2019, 60 (3) 400-406; DOI: 10.2967/jnumed.118.214403

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Evaluation of 111In-DOTA-5D3, a Surrogate SPECT Imaging Agent for Radioimmunotherapy of Prostate-Specific Membrane Antigen
Sangeeta Ray Banerjee, Vivek Kumar, Ala Lisok, Donika Plyku, Zora Nováková, Mary Brummet, Bryan Wharram, Cyril Barinka, Robert Hobbs, Martin G. Pomper
Journal of Nuclear Medicine Mar 2019, 60 (3) 400-406; DOI: 10.2967/jnumed.118.214403
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Keywords

  • SPECT/CT
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  • prostate cancer
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