[68Ga]Ga-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

Watts, Ankit; Singh, Baljinder; Singh, Harmandeep; Bal, Amanjit; Kaur, Harneet; Dhanota, Ninjit; Arora, Sunil; Mittal, Bhagwant Rai; Behera, Digambar

doi:10.1007/s00259-022-06059-2

Cited by 11 publications

(15 citation statements)

References 45 publications

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“…We have previously reported that 68 Ga-pentixafor has high specificity for imaging CXCR4 receptors in different variants of lung cancer and multiple myeloma patients. [13][14][15][16] In GBM, CXCR4 receptors have been reported to be overexpressing, which in turn is associated with tumor angiogenesis and poor survival. 19 An activation of ERK and PI3K/AKT signaling pathway by CXCR4/ CXCL12 presents highly promising molecular targets for developing new-targeted theranostics.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

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confidence: 99%

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

Waheed,

Singh,

Watts

et al. 2024

Clin Nucl Med

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Purpose The aim of this study was to evaluate the diagnostic potential of 68Ga-pentixafor PET/CT for in vivo CXCR4 receptors imaging in glioma and its possible role in response assessment to radiochemotherapy (R-CT). Methods Nineteen (12 men, 7 women) patients with glioblastoma multiforme (GBM) underwent 68Ga-pentixafor PET/CT, contrast-enhanced MR, and MR spectroscopy. Patients were divided in to 2 groups, that is, group I was the presurgical (n = 9) group in which the scanning was done before surgery, and PET findings were correlated with CXCR4 receptors’ density. The group II was the postsurgical (n = 10) group in which the scanning was done before and after R-CT and used for treatment response evaluation. The quantitative analysis of 68Ga-pentixafor PET/CT evaluated the mean SUVmax, SUVmean, SUVpeak, and T/B values. MR spectroscopy data evaluated the ratios of tumor metabolites (choline, NAA, creatine). Results 68Ga-Pentixafor uptake was noted in all (n = 19) the patients. In the group I, the mean SUVmax, SUVmean, SUVpeak, and T/B values were found to be 4.5 ± 1.6, 0.60 ± 0.26, 1.95 ± 0.8, and 6.9 ± 4.6, respectively. A significant correlation (P < 0.005) was found between SUVmean and choline/NAA ratio. Immunohistochemistry performed in 7/9 showed CXCR4 receptors’ positivity (intensity 3+; stained cells >50.0%). In the group II, the mean SUVmax at baseline was 4.6 ± 2.1 and did not differ (4.4 ± 1.6) significantly from the value noted at post–R-CT follow-up PET/CT imaging. At 6 months’ clinical follow-up, 4 patients showed stable disease. SUVmax and T/B ratios at follow-up imaging were lower (3.70 ± 0.90, 2.64 ± 1.35) than the corresponding values (4.40 ± 2.8; 2.91 ± 0.93) noted at baseline. Six (6/10) patients showed disease progression, and the mean SUVmax, and T/B ratio in these patients were significantly (P < 0.05) higher than the corresponding values at baseline and also higher than that noted in the stable patients. Conclusions 68Ga-Pentixafor PET/CT can be used for in vivo mapping of CXCR4 receptors in GBM. The technique after validation in a large cohort of patients may have added diagnostic value for the early detection of GBM recurrence and for treatment response evaluation.

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confidence: 99%

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confidence: 99%

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

Waheed,

Singh,

Watts

et al. 2024

Clin Nucl Med

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“…Regarding the possible future applications of [ 68 Ga] Ga-Pentixafor PET/CT, it may help us to provide patients with targeted therapy. Currently, preliminary experiences have been published considering the possibility of binding CXCR4 with therapeutic agents, such as Y-90 ([ 90 Y] Y-Pentixather) and Lu-177 ([ 177 Lu]Lu-Pentixather), the first-in-human one showing promising results in multiple myeloma patients [23]. However, although the potential has been discussed in the literature, far, there have been no reliable reports of Pentixather treatment use in solid tumors.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic value of [68Ga]Ga-Pentixafor versus [18F]FDG PET/CTs in non-small cell lung cancer: a head-to-head comparative study

Mirshahvalad

Manafi‐Farid

Fallahi

et al. 2023

Nuclear Medicine Communications

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Objective In this study, we aimed to compare the diagnostic value of [68Ga]Ga-Pentixafor and [18F]FDG PET/CT in the evaluation of non-small cell lung cancer (NSCLC) patients. Methods Patients with pathology-proven NSCLC were prospectively included. Patients underwent [18F]FDG and [68Ga]Ga-Pentixafor PET/CT within 1 week. All suspicious lesions were interpreted as benign or malignant, and the corresponding PET/CT semi-quantitative parameters were recorded. A two-sided P-value <0.05 was considered significant. Results Twelve consecutive NSCLC patients (mean age: 60 ± 7) were included. All patients underwent both [18F]FDG and [68Ga]Ga-Pentixafor PET/CT scans with a median interval of 2 days. Overall, 73 abnormal lesions were detected, from which 58 (79%) were concordant between [18F]FDG and [68Ga]Ga-Pentixafor PET/CT. All primary tumors were clearly detectable in both scans visually. Also, [68Ga]Ga-Pentixafor PET/CT demonstrated rather comparable results with [18F]FDG PET/CT scan in detecting metastatic lesions. However, malignant lesions demonstrated significantly higher SUVmax and SUVmean in [18F]FDG PET/CT (P-values <0.05). Regarding the advantages, [68Ga]Ga-Pentixafor depicted two brain metastases that were missed by [18F]FDG PET/CT. Also, a highly suspicious lesion for recurrence on [18F]FDG PET/CT scan was correctly classified as benign by subsequent [68Ga]Ga-Pentixafor PET/CT. Conclusion [68Ga]Ga-Pentixafor PET/CT was concordant with [18F]FDG PET/CT in detecting primary NSCLC tumors and could visualize the majority of metastatic lesions. Moreover, this modality was found to be potentially helpful in excluding tumoural lesions when the [18F]FDG PET/CT was equivocal, as well as in detecting brain metastasis where [18F]FDG PET/CT suffers from poor sensitivity. However, the count statistics were significantly lower.

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“…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].…”

Section: Discussionmentioning

confidence: 99%

“…Another 68 Ga-labelled PET imaging agent, that is, 68 Ga-Pentixafor, which targets the CXCR4 chemokine receptors over-expressed in over 30 different human cancers, has been developed. 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].…”

Section: Introductionmentioning

confidence: 99%

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

Jena,

Watts,

Aggarwal

et al. 2023

Nuclear Medicine Communications

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Objective To evaluate the diagnostic utility of 68Ga-Pentixafor PET/CT for in vivo imaging of CXCR4 receptors in soft tissue/bone sarcoma. Methods Ten (7M: 3F; mean age = 24.7 ± 14.2 years) consecutive patients with clinical and radiological evidence of bone/soft tissue sarcoma were recruited prospectively whole body 68Ga-Pentixafor PET/CT imaging was performed at 60-min after tracer administration. After performing standard CT, PET acquisition from head to toe was done (3 min/bed position) in a caudocranial direction. PET/CT data was reconstructed and SUVmax, SUVmean values, target-to-background ratio (TBR) and active tumor volume (cc) were computed for the tracer avid lesions. Histopathological and IHC analysis was performed on the surgically excised primary tumors. CXCR4 receptors’ intensity was evaluated by visual scoring. Results The mean SUVmax and SUVmean values in the primary tumors were 4.80 ± 1.0 (3.9–7.7) and 2.40 ± 0.60 (0.9–4.0). The mean TBR and tumor volume (cc) were 1.84 ± 1.3 and 312.2 ± 285. Diagnosis of osteosarcoma in 7, chondrosarcoma, leiomyosarcoma and synovial sarcoma in 1 patient each was confirmed on HP analysis. Distant metastatic lesions were seen in 3/10 patients. Nuclear CXCR4 receptors’ positivity was seen in 5, cytoplasmic in 4 and both pattern seen in 1 patient. The mean CXCR4 receptors’ intensity was found to be 7.6 ± 2. The highest SUVmax value of 7.7 was observed in the patient having both cytoplasmic and nuclear CXCR4 expression. SUVmax was found to be poorly correlated (r = 0.441) with CXCR4 expression. Conclusion 68Ga-Pentixafor PET/CT detects CXCR4 receptors over-expressed in sarcoma, its radio-theranostics potential needs detailed evaluation.

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[68Ga]Ga-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

Cited by 11 publications

References 45 publications

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

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

Diagnostic value of [68Ga]Ga-Pentixafor versus [18F]FDG PET/CTs in non-small cell lung cancer: a head-to-head comparative study

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

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