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

ABSTRACT: 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 (SUV_peak) 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 (SUV_peakSpleen 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 SUV_peakSpleen (<3.35) experienced a significantly shorter overall survival of 5 months as compared to 62 months in patients with a high SUV_peakSpleen >5.79 (P < 0.001). Multivariate Cox analysis confirmed SUV_peakSpleen 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.

SUBMITTER: Kraus S

PROVIDER: S-EPMC9373803 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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

Kraus Sabrina S Klassen Philipp P Kircher Malte M Dierks Alexander A Habringer Stefan S Gäble Alexander A Kortüm Klaus Martin KM Weinhold Niels N Ademaj-Kospiri Valëza V Werner Rudolf A RA Schirbel Andreas A Buck Andreas K AK Herhaus Peter P Wester Hans-Jürgen HJ Rosenwald Andreas A Weber Wolfgang A WA Einsele Hermann H Keller Ulrich U Rasche Leo L Lapa Constantin C

Theranostics 20220808 13

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 <sup>68</sup>Ga-Pentixafor uptake in multiple myel ...[more]

PMID: 35966583

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Project description:PurposeThis study aimed to explore the significance of 68Ga-pentixafor PET/CT in guiding surgical treatments for primary aldosteronism (PA) patients, by identifying functional lesions and determining the dominant side of aldosterone secretion.Materials and methodsWe prospectively included 91 PA patients receiving surgical treatments based on the results of 68Ga-pentixafor PET/CT. The 68Ga-pentixafor PET/CT images were evaluated by visual and semi-quantitative analysis. The relationship between radionuclide imaging characteristics and postoperative outcomes was assessed following surgery.ResultsThe positive detection rate of 68Ga-pentixafor PET/CT in 91 PA patients was 85.7 % (78/91) with a median maximum standardized uptake value (SUVmax) of 10.2 (6.0-16.0). The SUVmax was positively correlated with lesion diameter (r = 0.497, P < 0.001), while negatively correlated with the blood potassium level (r = -0.450, P < 0.001) and plasma renin activity (r = -0.297, P = 0.004). 63 cases of 73 PA patients with unilateral adrenal lesion were identified positive by 68Ga-pentixafor PET/CT, and 95.2 % of the 63 positive cases benefited from surgical resection of the identified positive lesions. Among 18 PA patients with bilateral lesions, 68Ga-pentixafor PET/CT identified positive lesions in 15 cases, and 86.7 % (13/15) of the positive cases benefited from total or partial adrenalectomy guided by 68Ga-pentixafor PET/CT. There was no significant difference in postoperative outcomes between patients undergoing partial adrenalectomy with those subjected to total adrenalectomy. The accuracy rate of 68Ga-pentixafor PET/CT in determining the dominant side of aldosterone secretion for PA was 85.7 %, which was comparable to the 71.4 % of adrenal vein sampling (AVS).Conclusions68Ga-pentixafor PET/CT could effectively guide the surgical management for PA patients, achieving favorable postoperative outcomes. The accuracy rate of 68Ga-pentixafor PET/CT in identifying the dominant side of aldosterone secretion was not inferior to that of AVS.

Project description:BackgroundC-X-C motif chemokine receptor 4 (CXCR4) is overexpressed in various solid cancers and can be targeted by CXCR4-directed molecular imaging. We aimed to characterize the in-vivo CXCR4 expression in patients affected with solid tumors, along with a comparison to ex-vivo findings.MethodsA total 142 patients with 23 different histologically proven solid tumors were imaged with CXCR4-directed PET/CT using [68 Ga]Ga-pentixafor (total number of scans, 152). A semi-quantitative analysis of the CXCR4-positive tumor burden including maximum standardized uptake values (SUVmax) and target-to-background ratios (TBR) using blood pool was conducted. In addition, we performed histopathological staining to determine the immuno-reactive score (IRS) from patients' tumor tissue and investigated possible correlations with SUVmax (by providing Spearman's rho ρ). Based on imaging, we also assessed the eligibility for CXCR4-targeted radioligand therapy or non-radioactive CXCR4 inhibitory treatment (defined as more than five CXCR4-avid target lesions [TL] with SUVmax above 10).ResultsOne hundred three of 152 (67.8%) scans showed discernible uptake above blood pool (TBR > 1) in 462 lesions (52 primary tumors and 410 metastases). Median TBR was 4.4 (1.05-24.98), thereby indicating high image contrast. The highest SUVmax was observed in ovarian cancer, followed by small cell lung cancer, desmoplastic small round cell tumor, and adrenocortical carcinoma. When comparing radiotracer accumulation between primary tumors and metastases for the entire cohort, comparable SUVmax was recorded (P > 0.999), except for pulmonal findings (P = 0.013), indicative for uniform CXCR4 expression among TL. For higher IRS, a weak, but statistically significant correlation with increased SUVmax was observed (ρ = 0.328; P = 0.018). In 42/103 (40.8%) scans, more than five TL were recorded, with 12/42 (28.6%) exhibiting SUVmax above 10, suggesting eligibility for CXCR4-targeted treatment in this subcohort.ConclusionsIn a whole-body tumor read-out, a substantial portion of prevalent solid tumors demonstrated increased and uniform [68 Ga]Ga-pentixafor uptake, along with high image contrast. We also observed a respective link between in- and ex-vivo CXCR4 expression, suggesting high specificity of the PET agent. Last, a fraction of patients with [68 Ga]Ga-pentixafor-positive tumor burden were rendered potentially suitable for CXCR4-directed therapy.

Project description:PurposeIn the characterization of severe lung diseases, early detection of specific inflammatory cells could help to monitor patients' response to therapy and increase chances of survival. Macrophages contribute to regulating the resolution and termination of inflammation and have increasingly been of interest for targeted therapies. [68Ga]Ga-DOTA-TATE is an established clinical radiopharmaceutical targeting somatostatin receptor subtype 2 (SSTR 2). Since activated macrophages (M1) overexpress SSTR 2, the aim of this study was to investigate the applicability of [68Ga]Ga-DOTA-TATE for positron emission tomography (PET) imaging of M1 macrophages in pulmonary inflammation.MethodsInflammation in the pig lungs was induced by warm saline lavage followed by injurious ventilation in farm pigs (n = 7). Healthy pigs (n = 3) were used as control. A 60-min dynamic PET scan over the lungs was performed after [68Ga]Ga-DOTA-TATE injection and [18F]FDG scan was executed afterward for comparison. The uptake of both tracers was assessed as mean standardized uptake values (SUVmean) 30-60-min post-injection. The PET scans were followed by computed tomography (CT) scans, and the Hounsfield units (HU) were quantified of the coronal segments. Basal and apical segments of the lungs were harvested for histology staining. A rat lung inflammation model was also studied for tracer specificity using lipopolysaccharides (LPS) by oropharyngeal aspiration. Organ biodistribution, ex vivo autoradiography (ARG) and histology samples were conducted on LPS treated, octreotide induced blocking and control healthy rats.ResultsThe accumulation of [68Ga]Ga-DOTA-TATE on pig lavage model was prominent in the more severely injured dorsal segments of the lungs (SUVmean = 0.91 ± 0.56), compared with control animals (SUVmean = 0.27 ± 0.16, p < 0.05). The tracer uptake corresponded to the damaged areas assessed by CT and histology and were in line with HU quantification. The [68Ga]Ga-DOTA-TATE uptake in LPS treated rat lungs could be blocked and was significantly higher compared with control group.ConclusionThe feasibility of the noninvasive assessment of tissue macrophages using [68Ga]Ga-DOTA-TATE/PET was demonstrated in both porcine and rat lung inflammation models. [68Ga]Ga-DOTA-TATE has a great potential to be used to study the role and presence of macrophages in humans in fight against severe lung diseases.

Project description:PurposeThe chemokine receptor CXCR4 is a promising target for molecular imaging of CXCR4+ cell types, e.g. inflammatory cells, in cardiovascular diseases. We speculated that a specific CXCR4 ligand, [68Ga]pentixafor, along with novel techniques for motion correction, would facilitate the in vivo characterization of CXCR4 expression in small culprit and nonculprit coronary atherosclerotic lesions after acute myocardial infarction by motion-corrected targeted PET/CT.MethodsCXCR4 expression was analysed ex vivo in separately obtained arterial wall specimens. [68Ga]Pentixafor PET/CT was performed in 37 patients after stent-based reperfusion for a first acute ST-segment elevation myocardial infarction. List-mode PET data were reconstructed to five different datasets using cardiac and/or respiratory gating. Guided by CT for localization, the PET signals of culprit and various groups of nonculprit coronary lesions were analysed and compared.ResultsEx vivo, CXCR4 was upregulated in atherosclerotic lesions, and mainly colocalized with CD68+ inflammatory cells. In vivo, elevated CXCR4 expression was detected in culprit and nonculprit lesions, and the strongest CXCR4 PET signal (median SUVmax 1.96; interquartile range, IQR, 1.55-2.31) was observed in culprit coronary artery lesions. Stented nonculprit lesions (median SUVmax 1.45, IQR 1.23-1.88; P = 0.048) and hot spots in naive remote coronary segments (median SUVmax 1.34, IQR 1.23-1.74; P = 0.0005) showed significantly lower levels of CXCR4 expression. Dual cardiac/respiratory gating provided the strongest CXCR4 PET signal and the highest lesion detectability.ConclusionWe demonstrated the basic feasibility of motion-corrected targeted PET/CT imaging of CXCR4 expression in coronary artery lesions, which was triggered by vessel wall inflammation but also by stent-induced injury. This novel methodology may serve as a platform for future diagnostic and therapeutic clinical studies targeting the biology of coronary atherosclerotic plaque.

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

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

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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