18F-FDG PET increases visibility of bone lesions in relapsed multiple myeloma: is this hypoxia-driven?

Abstract

INTRODUCTION:

Whole-body x-ray (WBX) is used for detecting skeleton abnormalities in patients with multiple myeloma (MM). An alternative might be 18F-FDG PET, which makes use of metabolic changes of malignant cells. The aims of this study were to evaluate whether 18F-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 (18F-FAZA) scan and immunohistochemical staining on bone marrow were performed to define whether FDG uptake coincides with angiogenesis-related tumor hypoxia.

PATIENTS AND METHODS:

18F-FDG PET (n = 44) and 18F-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 18F-FDG PET than on WBX (P = 0.000001). 18F-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 18F-FAZA scan results were negative.

CONCLUSIONS:

Our results demonstrate that 18F-FDG PET is relevant for diagnostic purposes compared with WBX in relapsing MM. The enhanced uptake of 18F-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 18F-FAZA-PET and HIF-1α expression.

• Authors: Esther G M de Waal, Riemer H J A Slart, Marnix J Leene, Philip M Kluin, Edo Vellenga
• Journal: Clinical nuclear medicine (Clin Nucl Med) Vol. 40 Issue 4 Pg. 291-6 (Apr 2015) ISSN: 1536-0229 [Electronic] United States
• PMID: 25546223 (Publication Type: Evaluation Study, Journal Article)

Chemical References

• Basic Helix-Loop-Helix Transcription Factors
• Glucose Transporter Type 1
• Glucose Transporter Type 3
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• Nitroimidazoles
• Radiopharmaceuticals
• SLC2A1 protein, human
• SLC2A3 protein, human
• Vascular Endothelial Growth Factor A
• Fluorodeoxyglucose F18
• endothelial PAS domain-containing protein 1
• fluoroazomycin arabinoside

Topics

• Basic Helix-Loop-Helix Transcription Factors (metabolism)
• Bone Marrow (metabolism, pathology)
• Bone Neoplasms (diagnostic imaging, metabolism, secondary)
• Cell Hypoxia
• Female
• Fluorodeoxyglucose F18
• Glucose Transporter Type 1 (metabolism)
• Glucose Transporter Type 3 (metabolism)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Male
• Middle Aged
• Multiple Myeloma (diagnostic imaging, metabolism, pathology)
• Nitroimidazoles
• Positron-Emission Tomography
• Radiopharmaceuticals
• Vascular Endothelial Growth Factor A (metabolism)