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Research ArticleOncology

A Microdosing Study with 99mTc-PHC-102 for the SPECT/CT Imaging of Primary and Metastatic Lesions in Renal Cell Carcinoma Patients

Oana C. Kulterer, Sarah Pfaff, Wolfgang Wadsak, Nathalie Garstka, Mesut Remzi, Chrysoula Vraka, Lukas Nics, Markus Mitterhauser, Franziska Bootz, Samuele Cazzamalli, Nikolaus Krall, Dario Neri and Alexander R. Haug
Journal of Nuclear Medicine March 2021, 62 (3) 360-365; DOI: https://doi.org/10.2967/jnumed.120.245530
Oana C. Kulterer
1Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
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Sarah Pfaff
1Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
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Wolfgang Wadsak
1Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
2Center of Biomarker Research in Medicine, Graz, Austria
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Nathalie Garstka
3Department of Urology, Medical University of Vienna, Vienna, Austria
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Mesut Remzi
3Department of Urology, Medical University of Vienna, Vienna, Austria
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Chrysoula Vraka
1Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
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Lukas Nics
1Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
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Markus Mitterhauser
1Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
4Ludwig Boltzmann Institute for Applied Diagnostics, Vienna, Austria
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Franziska Bootz
5Philochem AG, Otelfingen, Switzerland
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Samuele Cazzamalli
5Philochem AG, Otelfingen, Switzerland
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Nikolaus Krall
6Allcyte GmbH, Vienna, Austria
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Dario Neri
7Department of Chemistry and Applied Biosciences, ETH Zürich, Zürich, Switzerland; and
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Alexander R. Haug
1Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
8Christian Doppler Laboratory for Applied Metabolomics, Medical University of Vienna, Vienna, Austria
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Abstract

99mTc-PHC-102 is a 99mTc-labeled derivative of acetazolamide, a high-affinity small organic ligand of carbonic anhydrase IX (CAIX). 99mTc-PHC-102 has previously shown favorable in vivo biodistribution properties in mouse models of CAIX-positive clear cell renal cell carcinoma (ccRCC) and colorectal cancer. In this study, we aimed to explore the targeting performance of 99mTc-PHC-102 in SPECT in patients with renal cell carcinoma while also assessing the safety and tolerability of the radiotracer. Methods: We studied 5 patients with localized or metastatic ccRCC in a microdosing regimen, after the administration of a 50-μg total of CAIX ligand and 600–800 MBq of 99mTc-PHC-102. Tissue distribution and residence time in normal organs and tumors were analyzed by serial SPECT/CT scans at 3 time points (30 min, 2 h, and 6 h) after intravenous administration. Results: In the 5 patients studied, 99mTc-PHC-102 was well tolerated and no study drug–related adverse events were recorded. In the stomach, kidneys, and gallbladder, the radiotracer showed a rapid initial uptake, which cleared over time. Localization of the study drug in primary tumors of 5 patients was observed, with favorable tumor-to-background ratios. 99mTc-PHC-102 SPECT/CT allowed the identification of 4 previously unknown lung and lymph node metastases in 2 patients. Conclusion: 99mTc-PHC-102 is a promising SPECT tracer for the imaging of patients with ccRCC. This tracer has the potential to identify primary and metastatic lesions in different anatomic locations. 99mTc-PHC-102 might also serve as a companion diagnostic agent for future CAIX-targeting therapeutics.

  • clear cell renal cell carcinoma
  • carbonic anhydrase IX
  • SPECT
  • 99mTc
  • PHC-102

Footnotes

  • Published online Jul. 17, 2020.

  • © 2021 by the Society of Nuclear Medicine and Molecular Imaging.
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Journal of Nuclear Medicine: 62 (3)
Journal of Nuclear Medicine
Vol. 62, Issue 3
March 1, 2021
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A Microdosing Study with 99mTc-PHC-102 for the SPECT/CT Imaging of Primary and Metastatic Lesions in Renal Cell Carcinoma Patients
Oana C. Kulterer, Sarah Pfaff, Wolfgang Wadsak, Nathalie Garstka, Mesut Remzi, Chrysoula Vraka, Lukas Nics, Markus Mitterhauser, Franziska Bootz, Samuele Cazzamalli, Nikolaus Krall, Dario Neri, Alexander R. Haug
Journal of Nuclear Medicine Mar 2021, 62 (3) 360-365; DOI: 10.2967/jnumed.120.245530

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A Microdosing Study with 99mTc-PHC-102 for the SPECT/CT Imaging of Primary and Metastatic Lesions in Renal Cell Carcinoma Patients
Oana C. Kulterer, Sarah Pfaff, Wolfgang Wadsak, Nathalie Garstka, Mesut Remzi, Chrysoula Vraka, Lukas Nics, Markus Mitterhauser, Franziska Bootz, Samuele Cazzamalli, Nikolaus Krall, Dario Neri, Alexander R. Haug
Journal of Nuclear Medicine Mar 2021, 62 (3) 360-365; DOI: 10.2967/jnumed.120.245530
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Keywords

  • clear cell renal cell carcinoma
  • carbonic anhydrase IX
  • SPECT
  • 99mTc
  • PHC-102
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