Electron Spin Resonance Spectroscopy of Serum Albumin: A Novel New Test for Cancer Diagnosis and Monitoring

Abstract

Abstract Background: Proteins released by tumor cells can bind to serum albumin, leading to structural and functional modifications. We used electron spin resonance (ESR) spectroscopy to measure these changes in serum albumin and evaluate their utility for the diagnosis and monitoring of cancer. Methods: We used an ESR spectrometer and 16-doxyl stearic acid as spin probe to measure conformational changes in albumin in blood samples from a population of healthy donors and volunteers (n = 349), patients with a wide variety of hematologic and nonhematologic malignancy (n = 135), and patients with chronic diseases such as gastrointestinal and pulmonary disease, diabetes, and cirrhosis (n = 91). We added differing amounts of 16-doxyl stearic acid spin probe in ethanol to 50 μL of serum from each patient to create 3 different aliquots that differed in concentration of spin probe and ethanol, then incubated the aliquots for 10 min at 37 °C with continuous shaking. We measured the ESR spectra of each aliquot in triplicate and used proprietary software (MedInnovation GmbH) to evaluate the ESR spectrum for differences between cancer patients and the other groups. Results: The diagnostic sensitivity and specificity of this test were 87.4% and 95.7%, respectively, for differentiating healthy individuals from cancer patients and 87.4%, and 85.7% for differentiating cancer patients from chronic disease patients. Serial evaluation of albumin conformation changes in several patients followed during the course of their disease showed excellent agreement between the magnitude of abnormality in the ESR spectrum of albumin and clinical and pathologic estimates of disease severity. Conclusions: ESR spectroscopy of serum albumin is a sensitive and noninvasive technique that clearly demonstrates diagnostic utility in patients with cancer. This test also enables monitoring of the disease course through use of serial measurements.