⁶⁸Ga-Pentixafor PET/CT Demonstrating In Vivo CXCR4 Receptor Overexpression in Rare Lung Malignancies: Correlation with Histologic and Histochemical Findings

Abstract

Ga-pentixafor PET/CT imaging allows noninvasive assessment of C-X-C chemokine receptor type 4 (CXCR4) expression in various malignancies, but its use in rare lung cancer variants has not been reported. Methods: 68 Ga-pentixafor PET/CT imaging was performed on 6 patients (3 men, 3 women; mean age, 57.0 6 16.8 y) with suspected lung masses. Whole-body PET/CT images were acquired 1 h after intravenous injection of 148.0-185.0 MBq of the tracer. PET/CT images were reconstructed and analyzed. The image findings were correlated with histopathologic and quantitative (CXCR4) fluorescence-activated cell sorting analysis. Results: Histopathologic diagnosis of hemangioendothelioma, sarcomatoid carcinoma, and hemangiopericytoma was confirmed in 1 patient each. Lung metastasis was diagnosed in the remaining 3 of 6 patients with primary sarcoma (n 5 1), renal cell carcinoma (n 5 1), and unknown primary (n 5 1). Increased uptake in the primary lung mass, with an SUV max of 3.0, 6.34, and 13.0, was noted in the hemangiopericytoma, sarcomatoid carcinoma and hemangioendothelioma cases, respectively. The mean SUV max , mean fluorescence intensity, and percentage of stained cells were highest in hemangioendothelioma. Among 3 patients with lung metastases, the highest SUV max , 9.5, was in the primary sarcoma patient. Conclusion: 68 Ga-pentixafor selectively targets the in vivo whole-body disease burden of CXCR4 receptors. This approach thus holds promise for developing suitable radiotheranostics for lung cancers expressing these targets.

68Ga-Pentixafor PET/CT for in-vivo mapping of CXCR4 receptors as potential radiotheranostic targets in soft tissue and bone sarcoma: preliminary results

“…It has been reported that overexpression of CXCR4 receptors is responsible for tumour cell proliferation, migration and invasion in many human cancer types [36]. 68 Ga-Pentixafora PET tracer for in vivo targeting of CXCR4 receptors had been validated preclinically and in different human cancers [28][29][30][31][32]37]. CXCR4 expression has been reported to be up-regulated in osteosarcoma and plays an important role in distant metastases, thus, this class of chemokines present potential targets for theranostic applications [38].…”

“…A previous study in lung cancer showed similar results with the primary lung tumour mass (non-small cell lung cancer), showing higher SUV max (8.8) than metastatic lesions (brain and L4, 2.2 and 4.8, respectively) on 68 Ga-Pentixafor PET/CT imaging [29]. In another study, it was reported that the SUV max value in a patient with primary sarcoma, the lung metastatic lesion, showed an SUV max value of 9.5 [31].…”

“…68 Ga-Pentixafor PET/CT has shown promising results in some haematological and solid malignancies overexpressing the CXCR4 receptors [28][29][30]. 68 Ga-Pentixafor PET/CT has also been reported to show the feasibility of in vivo imaging of CXCR4 expression in sarcoma and its metastatic spread [31,32]. However, these two studies had only fewer numbers (1 and 4) of sarcoma patients in their mixed small series of all solid tumours taken together.…”

68Ga-Pentixafor PET/CT imaging for in-vivo CXCR4 receptor mapping in different lung cancer histologic sub-types: Correlation with quantitative receptors’ density by immunochemistry techniques

“…In a recent study, Watts et al reported that 68 Ga-Pentixafor PET/CT allows non-invasive assessment of CXCR4 expression in rare lung cancers i.e. haemangioendothelioma, sarcomatoid carcinoma and hemangiopericytoma and in lung metastasis cases [42]. The highest SUV max of 13.0 was noted in the case of haemangioendothelioma.…”

68Ga-Pentixafor PET/CT for In Vivo Imaging of CXCR4 Receptors in Glioma Demonstrating a Potential for Response Assessment to Radiochemotherapy: Preliminary Results

“…It has been reported that the tracer uptake is preferentially tied with the CXCR4 receptors, which are overexpressed in many cancers and have yielded promising in vivo PET imaging results in lung cancer, multiple myeloma, and glioma. [13][14][15][16][17] In the present study, 68 Ga-pentixafor PET/CTwas performed for imaging CXCR4 receptors' in GBM patients with primary or recurrent/residual disease and used for response assessment to radiochemotherapy (R-CT). The image findings were corroborated with tumor CXCR4 receptors' density and the quantitative MR spectroscopy (MRS) parameters.…”