Interobserver Agreement Rates on C-X-C Motif Chemokine Receptor 4-Directed Molecular Imaging and Therapy.

Background: We aimed to evaluate the interobserver agreement rates in patients scanned with C-X-C motif chemokine receptor 4 (CXCR4)-directed PET/CT, including the rate of patients eligible for CXCR4-targeted radioligand therapy (RLT) based on scan results.
Methods: Four independent observers reviewed 50 CXCR4-targeted [ 68 Ga]pentixafor PET/CT of patients with various solid cancers. On a visual level, the following items were assessed by each reader: overall scan impression, number of organ and lymph node (LN) metastases and number of affected organs and LN regions. For a quantitative investigation, readers had to choose a maximum of 3 target lesions, defined as largest in size and/or most intense uptake per organ compartment. Reference tissues were also quantified, including unaffected hepatic parenchyma and blood pool. Last, all observers had to decide whether patients were eligible for CXCR4-targeted RLT. Concordance rates were tested using intraclass correlation coefficients (ICCs). For interpretation, we applied the definition of Cicchetti (with 0.4-0.59 indicating fair; 0.6-0.74, good; 0.75-1, excellent agreement).
Results: On a visual level, fair agreement was achieved for an overall scan impression (ICC, 0.58; 95% confidence interval, 0.45-0.71). Organ and LN involvement (ICC, ≥0.4) demonstrated fair, whereas CXCR4 density and number of LN and organ metastases showed good agreement rates (ICC, ≥0.65). Number of affected organs and affected LN areas, however, showed excellent concordance (ICC, ≥0.76). Quantification in LN and organ lesions also provided excellent agreement rates (ICC, ≥0.92), whereas quantified uptake in reference organs provided fair concordance (ICC, ≥0.54). Again, excellent agreement rates were observed when deciding on patients eligible for CXCR4-RLT (ICC, 0.91; 95% confidence interval, 0.85-0.95).
Conclusions: In patients scanned with CXCR4-targeted PET/CT, we observed fair to excellent agreement rates for both molecular imaging and therapy parameters, thereby favoring a more widespread adoption of [ 68 Ga]pentixafor in the clinic.
Competing Interests: Conflicts of interest and sources of funding: This project was partially supported by the Okayama University “RECTOR” Program, KAKENHI grant (21K19450) from the Japan Society for the Promotion of Science (T.H.) and the German Research Foundation (507803309, R.A.W.; 453989101, R.A.W., T.H.). R.A.W. and A.K.B. have received speaker's honoraria from PentixaPharm. A.K.B. is a member of the advisory board of PentixaPharm. R.A.B. is consultant to and has received speaker's honoraria from Bayer Healthcare (Leverkusen, Germany) and Eisai GmbH (Frankfurt, Germany). The other authors have no conflicts to report.
(Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)