Use of Biomarkers of Inflammation in the Differentiation of Iron Deficiency and Anaemia-Lessons from Inflammatory Bowel Disease.

Iron deficiency and iron deficiency anaemia are common in inflammatory bowel disease (IBD), to the detriment of the patients' quality of life. Since ferritin, as an acute-phase protein (APP), has limited diagnostic value in IBD, concurrent assessment of C-reactive protein (CRP) is recommended. The World Health Organization suggests using α1-acid glycoprotein (AGP) as an additional biomarker due to its differing half-life. This study aimed to evaluate ferritin levels in patients with IBD using CRP and AGP, individually and in combination. A total of 118 patients with IBD (mean age: 45.48 ± 15.25 years, 47.46% female) were recruited, including 38 with Crohn's disease, 47 with ulcerative colitis, and 33 controls. The results showed that while CRP alone detected an inflammatory increase in ferritin of 29.76%, this increased to 82.14% when AGP or both AGP and CRP were considered (p < 0.05). Elevated AGP levels were more prevalent in patients with ulcerative colitis. However, concordance between high CRP and AGP levels was confirmed in only 55% of cases. Correcting for inflammation using CRP and/or AGP significantly improved the diagnostic accuracy of ferritin levels in patients with IBD, highlighting the challenge posed by inflammation when assessing iron deficiency.

Reduced splenic uptake on 68Ga-Pentixafor-PET/CT imaging in multiple myeloma - a potential imaging biomarker for disease prognosis.

Beyond being a key factor for tumor growth and metastasis in human cancer, C-X-C motif chemokine receptor 4 (CXCR4) is also highly expressed by a number of immune cells, allowing for non-invasive read-out of inflammatory activity. With two recent studies reporting on prognostic implications of the spleen signal in diffusion-weighted magnetic resonance imaging in patients with plasma cell dyscrasias, the aim of this study was to correlate splenic 68Ga-Pentixafor uptake in multiple myeloma (MM) with clinical parameters and to evaluate its prognostic impact. Methods: Eighty-seven MM patients underwent molecular imaging with 68Ga-Pentixafor-PET/CT. Splenic CXCR4 expression was semi-quantitatively assessed by peak standardized uptake values (SUVpeak) and corresponding spleen-to-bloodpool ratios (TBR) and correlated with clinical and prognostic features as well as survival parameters. Results:68Ga-Pentixafor-PET/CT was visually positive in all MM patients with markedly heterogeneous tracer uptake in the spleen. CXCR4 expression determined by 68Ga-Pentixafor-PET/CT corresponded with advanced disease and was inversely associated with the number of previous treatment lines as compared to controls or untreated smouldering multiple myeloma patients (SUVpeakSpleen 4.06 ± 1.43 vs. 6.02 ± 1.16 vs. 7.33 ± 1.40; P < 0.001). Moreover, reduced splenic 68Ga-Pentixafor uptake was linked to unfavorable clinical outcome. Patients with a low SUVpeakSpleen (<3.35) experienced a significantly shorter overall survival of 5 months as compared to 62 months in patients with a high SUVpeakSpleen >5.79 (P < 0.001). Multivariate Cox analysis confirmed SUVpeakSpleen as an independent predictor of survival (HR 0.75; P = 0.009). Conclusion: These data suggest that splenic 68Ga-Pentixafor uptake might provide prognostic information in pre-treated MM patients similar to what was reported for diffusion-weighted magnetic resonance imaging. Further research to elucidate the underlying biologic implications is warranted.

Investigation of spleen CXCR4 expression by [68Ga]Pentixafor PET in a cohort of 145 solid cancer patients.

BACKGROUND: The chemokine receptor CXCR4 is frequently overexpressed and associated with adverse prognosis in most hematopoietic malignancies and solid cancers. Recently, CXCR4 molecular imaging using the CXCR4-specific positron emission tomography (PET) tracer Pentixafor ([68Ga]Pentixafor) has become a well-established method to non-invasively measure CXCR4 expression in vivo. In previous Pentixafor imaging studies, highly variable CXCR4 tracer uptake to the spleen was observed. RESULTS: We investigated the hypothesis that enhanced spleen [68Ga]Pentixafor uptake and thus CXCR4 expression in patients with solid tumors would indicate an activated spleen state and/or an association with clinical and prognostic features and survival parameters. In this retrospective study, [68Ga]Pentixafor-PET images and patient records of 145 solid tumor patients representing 27 cancer entities were investigated for an association of spleen [68Ga]Pentixafor uptake and clinical characteristics and outcome. Based on this assessment, we did not observe differences in clinical outcomes, measured by progression-free survival, overall survival and remission status neither within the entire cohort nor within subgroups of adrenal cancer, desmoplastic small round cell tumor, neuroendocrine tumors, non-small cell lung cancer, small cell lung cancer and pancreatic adenocarcinoma patients. No tumor entity showed especially high levels of spleen [68Ga]Pentixafor uptake compared to others or a control cohort. However, when investigating laboratory parameters, there was a positive correlation of high spleen [68Ga]Pentixafor uptake with leukocyte and/or platelet counts in neuroendocrine tumors, non-small cell lung cancer and small cell lung cancer. CONCLUSION: Spleen [68Ga]Pentixafor uptake was not associated with stage of disease and clinical outcomes in solid tumor patients. We identified positively associated platelet and/or leukocyte counts with spleen [68Ga]Pentixafor uptake in neuroendocrine tumors, non-small cell lung cancer and small cell lung cancer, suggesting that splenic CXCR4 expression could possibly play a role in systemic immunity/inflammation in some types of solid tumors or a subgroup of patients within solid tumor entities.