[⁶⁸Ga]Pentixafor-PET/CT for imaging of chemokine receptor CXCR4 expression in multiple myeloma - Comparison to [¹⁸F]FDG and laboratory values

Abstract

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 [ 68 Ga]Pentixafor in MM and a potential role for stratifying patients to CXCR4-directed therapies. Thirty-five patients with MM underwent [ 68 Ga]Pentixafor-PET/CT for evaluation of eligibility for endoradiotherapy. In 19/35 cases, [ 18 F]FDG-PET/CT for correlation was available. Scans were compared on a patient and on a lesion basis. Tracer uptake was correlated with standard clinical parameters of disease activity.[ 68 Ga]Pentixafor-PET detected CXCR4-positive disease in 23/35 subjects (66%). CXCR4-positivity at PET was independent from myeloma subtypes, cytogenetics or any serological parameters and turned out as a negative prognostic factor. In the 19 patients in whom a comparison to [ 68 Ga]Pentixafor-PET provides further evidence that CXCR4 expression frequently occurs in advanced multiple myeloma, representing a negative prognostic factor and a potential target for myeloma specific treatment. However, selecting patients for CXCR4 directed therapies and prognostic stratification seem to be more relevant clinical applications for this novel imaging modality, rather than diagnostic imaging of myeloma.

CXCR4 Ligands: The Next Big Hit?

“…Additionally, chemokine receptor expression on the cell surface has been shown to be a dynamic process that is responsive to concomitant or intermittent therapy (Constantin Lapa, unpublished data, 2017). Future studies should investigate the underlying mechanisms and biologic implications (76). So far, the main value of CXCR4 imaging in oncology is not staging of disease but identification of suitable candidates for chemokine receptortargeted treatment, including radiolabeled and nonradiolabeled options.…”

“…So far, the main value of CXCR4 imaging in oncology is not staging of disease but identification of suitable candidates for chemokine receptortargeted treatment, including radiolabeled and nonradiolabeled options. Most available data concern multiple myeloma, with about two thirds of patients having CXCR4-positive disease (76). Recently, a peptide ligand that can be labeled with a-or b-emitters (pentixather) and that represents a therapeutic counterpart to the diagnostic PET/SPECT agents was developed (86).…”

Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach

“…Recently, Wester and coworkers developed the theranostic agents [ 68 Ga]Pentixafor and [ 177 Lu]/[ 90 Y]Pentixather for non-invasive assessment of CXCR4 expression and subsequent chemokine-directed endoradiotherapy (ERT) 13-23.…”

Side Effects of CXC-Chemokine Receptor 4–Directed Endoradiotherapy with Pentixather Before Hematopoietic Stem Cell Transplantation

“…177 Lu-pentixather has already been proven capable of successfully eradicating CXCR4-positive tumor cells without completely and irreversibly destroying the supporting HSPC niche in a preclinical endoradiotherapy mouse model-a capability that is a prerequisite for the reconstitution of the hematopoietic system after therapy. Moreover, first-in-human experiences of CXCR4-directed endoradiotherapy with pentixather in patients with advanced-stage multiple myeloma, acute myeloid leukemia, and non-Hodgkin lymphoma have shown the feasibility of this therapy in combination with high-dose chemotherapy and autologous or allogeneic hematopoietic stem cell transplantation (HSCT) (10,(15)(16)(17). However, because of the high expression levels of CXCR4 on HSPCs and its crucial function in their regulation, the safety of CXCR4-directed endoradiotherapy has to be further studied.…”