In:
Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 2014-2014
Abstract:
Chemokine receptors form a large family of G-protein coupled receptors that mediate chemotaxis of cells towards a gradient of chemokines. The C-X-C chemokine receptor-4 (CXCR4, also known as fusin, CD184) exerts its biological effects by binding its ligand CXCL12 (or Stromal-cell derived factor-1, SDF-1) which activates downstream pathways, ultimately resulting in altered cell adhesion and cell homing. Physiologically, the CXCR4/CXCL12 interaction plays a pivotal role in the recruitment and homing of hematopoietic stem/ progenitor cells (HSPC) and immune cells. In cancer, CXCR4 expression is associated with tumor dissemination and prognosis. Using multiple myeloma (MM) as an exemplary CXCR4-expressing cancer entity, we report the evaluation of [68Ga]Pentixafor-PET as a method for in vivo mapping of CXCR4 expression density by means of Positron Emission Tomography. [68Ga] Pentixafor-PET provides images with excellent specificity and contrast when assessed in mice xenografted with human CXCR4-positive MM. We next analyzed CXCR4 expression using [68Ga]Pentixafor-PET in a cohort of fourteen patients with advanced MM. These patients also underwent standard [18F] Fluoro-Deoxyglucose-PET (FDG-PET). Nine of fourteen FDG-PET scans were rated visually positive, whereas ten of fourteen Pentixafor-PET scans revealed MM manifestations. Assessment of blood counts and standard CD34+ flow cytometry did not reveal significant blood count changes or alterations in HSPC frequency associated with tracer application. These data document the first methodology for clinical PET imaging of CXCR4 in a cohort of MM patients. [68Ga]Pentixafor-PET opens a broad field of clinical investigations on CXCR4 expression and regulation in the cancer field and beyond. Disclosures Wester: SCINTOMICS, 〉 Radiopharmaceutical Technology: Employment.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood.V124.21.2014.2014
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2014
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
