PT  - JOURNAL ARTICLE
AU  - Helisch, Andreas
AU  - Kratochwil, Clemens
AU  - Kleist, Christian
AU  - Krämer, Susanne
AU  - Rosales Castillo, Juan Jose
AU  - Dendl, Katharina
AU  - Rathke, Hendrik
AU  - von Goetze, Isabelle
AU  - Schreckenberger, Mathias
AU  - Jäger, Dirk
AU  - Lindner, Thomas
AU  - Mier, Walter
AU  - Giesel, Frederik
AU  - Haberkorn, Uwe
AU  - Röhrich, Manuel
TI  - Feasibility, Tolerability, and Preliminary Clinical Response of Fractionated Radiopharmaceutical Therapy with <sup>213</sup>Bi-FAPI-46: Pilot Experience in Patients with End-Stage, Progressive Metastatic Tumors
AID  - 10.2967/jnumed.124.268386
DP  - 2024 Oct 30
TA  - Journal of Nuclear Medicine
PG  - jnumed.124.268386
4099  - http://jnm.snmjournals.org/content/early/2024/10/30/jnumed.124.268386.short
4100  - http://jnm.snmjournals.org/content/early/2024/10/30/jnumed.124.268386.full
AB  - Radiopharmaceutical therapies (RPTs) based on fibroblast activation protein (FAP) and FAP inhibitors (FAPIs) are a new option for progressive metastatic cancer in patients pretreated multiple times. To date, published in-human data refer to initial experiences with β-emitting 90Y- and 177Lu-based RPT. However, the short tumor retention time of FAPI ligands is considered a major limitation of FAPI RPT. Therefore, fractionated FAPI RPT with 213Bi, an α-emitter with a half-life of 46 min, appears to be a promising FAPI RPT regimen. Here, we report on our initial experiences with regard to the feasibility, tolerability, and response of fractionated 213Bi-FAPI-46 RPT. Methods: Six patients (4 women and 2 men) with progressive metastatic solid tumors (3 colon cancer, 1 anal cancer, 1 breast cancer, and 1 prostate cancer) aged 16–77 y were treated with a mean of 1,609 MBq of 213Bi-FAPI-46, fractionated into 53 single applications (range, 5–12 RPT applications per patient; mean, 8.8 applications) over a period of up to 107 h per patient. Of the 6 patients, 4 patients received adjuvant treatment with pembrolizumab. 18F-FDG (4 patients) and 68Ga-FAPI-46 (5 patients) PET/CT scans were performed before and after RPT. PET images were assessed visually and by calculating total lesion glycolysis and total lesion FAPI. Results: RPT with 213Bi-FAPI-46 was well tolerated without adverse side effects. In terms of visual response assessment, there was 1 partial response (16.7%), 1 patient with stable disease (16.7%), and 4 patients with progressive disease (66.7%). Concordantly, total lesion glycolysis and total lesion FAPI were decreased in the responding patient (not applicable and −24.3%, respectively), slightly decreased in the patient with stable disease (−10.6% and −5.9%, respectively), and increased in the 4 patients with progression (mean, +104.4% and +321.3%, respectively). Conclusion: Fractionated FAPI RPT with the short-half-life α-emitter 213Bi-FAPI-46 is a promising approach that matches the pharmacokinetics of FAPI-46 better than the 177Lu- or 90Y-labeled compounds. In this pilot project, fractionated RPT with 213Bi-FAPI-46 showed good clinical tolerability and even led to regressive or stable disease in the short term in 2 of 6 patients. Further studies with larger patient cohorts are required to evaluate the actual efficacy and long-term effects of this variant of FAPI RPT.