Chemokine (C-X-C motif) receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer including multiple myeloma (MM). Proof-of-concept of CXCR4-directed radionuclide therapy in MM has recently been reported. This study assessed the diagnostic performance of the CXCR4-directed radiotracer [⁶⁸Ga]Pentixafor in MM and a potential role for stratifying patients to CXCR4-directed therapies.

Given its prominent role in inflammation and cancer biology, the C-X-C motif chemokine receptor 4 (CXCR4) has gained a lot of attention in the recent years. This review gives a short overview of the physiology and pathology of chemokines and chemokine receptors and then focuses on the current experience of targeting CXCR4, using radiolabeled receptor ligands suitable for positron emission tomography (PET) imaging, in both hematologic and solid malignancy as well as in inflammatory conditions. Additionally, CXCR4-directed endoradiotherapy (ERT) as a new treatment option is discussed.

Background: Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) with ¹⁷⁷Lu-labeled PSMA ligands has achieved remarkable results in advanced disease stages of metastatic castration-resistant prostate cancer (mCRPC). However, not all patients benefit from this therapy. Different treatment responses could be explained by tumor heterogeneity triggered by progression and the number of prior treatments. PSMA-negative lesions can be missed on PSMA ligand PET/CT, which subsequently results in an underestimation of tumor burden. Conversely, high FDG uptake may also be an indicator of tumor aggressiveness and thus a poor prognostic marker for response to RLT and overall survival (OS). The aim of this analysis was to investigate the prognostic value of combined PSMA ligand PET/CT and [¹⁸F]fluorodeoxyglucose (FDG) PET/CT for outcome prediction in patients undergoing RLT. Materials and methods: This bicentric analysis included 54 patients with mCRPC who underwent both FDG and PSMA ligand PET/CT imaging before RLT. In all patients, the pattern of PSMA ligand and FDG uptake was visually assessed. Patients with at least one FDG-positive, but PSMA-negative (FDG+/PSMA−) lesions were compared to patients without any FDG+/PSMA− lesions. A log-rank analysis was used to assess the difference in OS between subgroups. Results: Median OS was 11 ± 1.8 months (95% CI 7.4–14.6). A significantly lower OS (p < 0.001) was found in patients with at least one FDG+/PSMA− lesion at baseline PET/CTs (n = 18) with a median OS of 6.0 ± 0.5 months (95% CI: 5.0–7.0 months). In comparison, patients without any FDG+/PSMA− lesions (n = 36) had a median OS of 16.0 ± 2.5 months (95% CI: 11.2–20.8 months). Conclusion: FDG+/PSMA− lesions are a negative predictor of overall survival in patients with mCRPC undergoing RLT. However, it remains to be determined if patients with FDG+/PSMA− lesions should be excluded from PSMA RLT.

[ 68 Ga]Pentixafor-PET/CT for imaging of chemokine receptor 4 expression in small cell lung cancer - initial experience