18F-FDG PET Increases Visibility of Bone Lesions in Relapsed Multiple Myeloma: Is This Hypoxia-Driven?

INTRODUCTION: Whole-body x-ray (WBX) is used for detecting skeleton abnormalities in patients with multiple myeloma (MM). An alternative might be F-FDG PET, which makes use of metabolic changes of malignant cells. The aims of this study were to evaluate whether F-FDG PET detects more lesions compared with WBX in patients with relapsing MM and to define its prognostic value. In addition 1-α-D: -(5-deoxy-5-[F]-fluoroarabinofuranosyl)-2-nitroimidazole (F-FAZA) scan and immunohistochemical staining on bone marrow were performed to define whether FDG uptake coincides with angiogenesis-related tumor hypoxia.

PATIENTS AND METHODS: F-FDG PET (n = 44) and F-FAZA-PET (n = 5) were performed in patients with relapsed MM. Bone marrow biopsies (n = 20) were evaluated for hypoxia inducible factors (HIF) 1α and 2α, vascular endothelial growth factor, glucose transport proteins 1 and 3, and the microvessel density.

RESULTS: New lesions were more frequently demonstrated on F-FDG PET than on WBX (P = 0.000001). F-FDG PET was not predictive for progression-free survival and overall survival. Immunohistochemical staining on bone marrow biopsies demonstrated a significant increase in microvessel density and elevated expression of vascular endothelial growth factor, HIF-2α, and glucose transport protein 3 by the malignant plasma cells. However, HIF-1α expression and F-FAZA scan results were negative.

CONCLUSIONS: Our results demonstrate that F-FDG PET is relevant for diagnostic purposes compared with WBX in relapsing MM. The enhanced uptake of F-FDG PET is likely related to the activation of the HIF-2α signaling pathway but probably independent of hypoxia-induced signaling in view of the negative findings on both F-FAZA-PET and HIF-1α expression.