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

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).

Fig. 1

Example of maximum intensity projections 3, 11, 18, 30, 40, and 60 min post-tracer administration (p.a) showing in-patient ¹⁸F-Azafol activity distribution

Fig. 2

Typical ¹⁸F-AzaFol uptake pattern in the choroid plexuses (lateral ventricles) for a representative patient at 30 min post-administration

Fig. 3

Biological organ kinetic of ¹⁸F-AzaFol corrected for ¹⁸F physical decay. Color bars represent the average percent of injected activity per gram of tissue (%IA/g) ± 1SD, for each time point

Fig. 4

Mean nA ± SD (average values and SD evaluated across the 6 patients), for considered source organs. Mono- and bi-exponential fits of experimental data are displayed in addition to the tail according to pure physical decay to infinity for t > 60 min. For sake of visibility, the time base in each source organ graph was restricted to three times the physical half-life of ¹⁸F