Radiation dosimetry of 18F-AzaFol: A first in-human use of a folate receptor PET tracer

Silvano Gnesin; Joachim Müller; Irene A Burger; Alexander Meisel; Marco Siano; Martin Früh; Matthias Choschzick; Cristina Müller; Roger Schibli; Simon M Ametamey; Philipp A Kaufmann; Valerie Treyer; John O Prior; Niklaus Schaefer

doi:10.1186/s13550-020-00624-2

Radiation dosimetry of ¹⁸F-AzaFol: A first in-human use of a folate receptor PET tracer

EJNMMI Res. 2020 Apr 8;10(1):32. doi: 10.1186/s13550-020-00624-2.

Authors

Silvano Gnesin¹, Joachim Müller², Irene A Burger^{3

4}, Alexander Meisel^{3

5

6}, Marco Siano⁷, Martin Früh^{7

8}, Matthias Choschzick⁹, Cristina Müller^{5

10}, Roger Schibli^{5

10}, Simon M Ametamey⁵, Philipp A Kaufmann³, Valerie Treyer³, John O Prior¹¹, Niklaus Schaefer¹²

Affiliations

¹ Institute of Radiation Physics, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
² Department of Radiology and Nuclear Medicine, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
³ Department of Nuclear Medicine, University Hospital of Zurich, Zurich, Switzerland.
⁴ Department of Nuclear Medicine, Kantonsspital Baden, Baden, Switzerland.
⁵ Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
⁶ Department of Internal Medicine-Hematology & Oncology, Stadtspital Waid, Zurich, Switzerland.
⁷ Department of Oncology and Hematology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
⁸ University of Bern, Bern, Switzerland.
⁹ Institute for Pathology and Molecular Pathology, University Hospital of Zurich, Zurich, Switzerland.
¹⁰ Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Villigen, Switzerland.
¹¹ Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital and University of Lausanne, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland. [email protected].
¹² Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital and University of Lausanne, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland.

Abstract

Background: The folate receptor alpha (FRα) is an interesting target for imaging and therapy of different cancers. We present the first in-human radiation dosimetry and radiation safety results acquired within a prospective, multicentric trial (NCT03242993) evaluating the ¹⁸F-AzaFol (3'-aza-2'-[¹⁸F]fluorofolic acid) as the first clinically assessed PET tracer targeting the FRα.

Material and methods: Six eligible patients presented a histologically confirmed adenocarcinoma of the lung with measurable lesions (≥ 10 mm according to RECIST 1.1). TOF-PET images were acquired at 3, 11, 18, 30, 40, 50, and 60 min after the intravenous injection of 327 MBq (range 299-399 MBq) of ¹⁸F-AzaFol to establish dosimetry. Organ absorbed doses (AD), tumor AD, and patient effective doses (E) were assessed using the OLINDA/EXM v.2.0 software and compared with pre-clinical results.

Results: No serious related adverse events were observed. The highest AD were in the liver, the kidneys, the urinary bladder, and the spleen (51.9, 45.8, 39.1, and 35.4 μGy/MBq, respectively). Estimated patient and gender-averaged E were 18.0 ± 2.6 and 19.7 ± 1.4 μSv/MBq, respectively. E in-human exceeded the value of 14.0 μSv/MBq extrapolated from pre-clinical data. Average tumor AD was 34.8 μGy/MBq (range 13.6-60.5 μGy/MBq).

Conclusions: ¹⁸F-Azafol is a PET agent with favorable dosimetric properties and a reasonable radiation dose burden for patients which merits further evaluation to assess its performance.

Trial registration: ClinicalTrial.gov, NCT03242993, posted on August 8, 2017.

Keywords: 18F-Azafol; Choroid plexuses; Dosimetry; FOLR1; FRalpha; FRα; Folate receptor; Imaging; Lung cancer; OLINDA/EXM; Positron emission tomography (PET).

Associated data

ClinicalTrials.gov/NCT03242993

Abstract

Associated data

Grants and funding