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Development of a Novel Imaging Agent for Determining Albumin Uptake in Solid Tumors

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Abstract

Purpose

The purpose of this study was to investigate the albumin-binding compound 111In-C4-DTPA as an imaging agent for the detection of endogenous albumin accumulation in tumors.

Methods

111In-C4-DTPA was injected in healthy nude mice for pharmacokinetic and biodistribution studies (10 min, 1, 6, 24, and 48 h, n = 4) and subsequently in tumor-bearing mice for single-photon emission computed tomography/X-ray-computed tomography (SPECT/CT) imaging studies. Four different human tumor xenograft models (LXFL529, OVXF899, MAXFTN401, and CXF2081) were implanted subcutaneously unilaterally or bilaterally (n = 4–8). After intravenous administration of 111In-C4-DTPA, SPECT/CT images were collected over 72 h at 4–6 time points. Additionally, gamma counting was performed for the blood, plasma, lungs, heart, liver, spleen, kidneys, muscle, and tumors at 72 h post-injection.

Results

111In-C4-DTPA bound rapidly to circulating albumin upon injection, and the radiolabeled albumin conjugate thus formed was stable in murine and human serum. SPECT/CT images demonstrated a time-dependent uptake with a maximum of 2.7–3.8% ID/cm3 in the tumors at approximately 24 h post-injection and mean tumor/muscle ratios in the range of 3.2–6.2 between 24 and 72 h post-injection. The kidneys and bladder were the predominant elimination organs. Gamma counting at 72 h post-injection showed 1.3–2.5% ID/g in the tumors and mean tumor/muscle ratios in the range of 4.9–9.4.

Conclusion

111In-C4-DTPA bound rapidly to circulating albumin upon injection and showed time-dependent uptake in the tumors demonstrating a potential for clinical application as a companion imaging diagnostic for albumin-binding anticancer drugs.

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Author notes

  1. S. Daum and J. P. Magnusson contributed equally to this work.

Authors and Affiliations

  1. Centurion Biopharma Corporation/CytRx Drug Discovery Branch, Engesserstr. 4, 79108, Freiburg, Germany

    S. Daum, J. P. Magnusson, L. Pes, J. Garcia Fernandez, S. Chercheja, F. Medda, F. I. Nollmann, S. D. Koester, P. Perez Galan, A. Warnecke, K. Abu Ajaj & Felix Kratz

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  1. S. Daum
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  2. J. P. Magnusson
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  3. L. Pes
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  4. J. Garcia Fernandez
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  12. Felix Kratz
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Corresponding author

Correspondence to Felix Kratz.

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Conflict of Interest

Steffen Daum, Johannes Pall Magnusson, Lara Pes, Javier Garcia Fernandez, Serghei Chercheja, Federico Medda, Friederike Inga Nollmann, Stephan David Koester, Patricia Perez Galan, Anna Warnecke, Khalid Abu Ajaj, and Felix Kratz declare no conflict of interest.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Informed Consent

The institutional review board of our institute approved this retrospective study, and the requirement to obtain informed consent was waived.

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Electronic Supplementary Material

Synthesis and lyophilization protocol for the maleimide-bearing DTPA chelating agent, C4-DTPA and the albumin conjugate, C4-DTPA-Albumin; radiolabeling and radiochemical purity determination of 111In-C4-DTPA; albumin-binding properties of 111In-C4-DTPA in human and murine serum; 2D SPECT/CT data of all experiments are depicted in the Supplementary Material.

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Daum, S., Magnusson, J.P., Pes, L. et al. Development of a Novel Imaging Agent for Determining Albumin Uptake in Solid Tumors. Nucl Med Mol Imaging 53, 189–198 (2019). https://doi.org/10.1007/s13139-019-00587-w

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  • DOI: https://doi.org/10.1007/s13139-019-00587-w

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