Imaging CXCR4 receptors expression for staging multiple myeloma by using 68Ga-Pentixafor PET/CT: comparison with 18F-FDG PET/CT

Shekhawat, Amit Singh; Singh, Baljinder; Malhotra, Pankaj; Watts, Ankit; Basher, Rajender Kumar; Kaur, Harneet; Hooda, Monika; Radotra, Bishan Das

doi:10.1259/bjr.20211272

Cited by 21 publications

(17 citation statements)

References 37 publications

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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%

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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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Section: Discussionmentioning

confidence: 99%

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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“…CXCR4 stromal cell derived 1-α factor is critical in cancer growth and metastasis. Typically, the rising activity of this factor in lymph nodes, bone, bone marrow, lung and liver has been reported to trigger the metastasis of CXCR4 expressing tumor cells [24][25]. CXCR4 receptors' over-expression thus has been recognized as an adverse prognostic factor in various malignancies including lung cancer [26-28].…”

Section: Discussionmentioning

confidence: 99%

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

Watts

Singh

et al. 2022

Preprint

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Purpose In-vivo CXCR4 receptor quantification in different lung cancer (LC) sub-types using 68Ga-Pentixafor PET/CT and correlation with quantitative CXCR4-receptors’ tissue density by immunochemistry analyses. Methods 68Ga-Pentixafor PET/CT imaging was performed prospectively in 94 (77M: 17F, mean age 60.15 ± 10.12 yrs) LC patients. CXCR4 receptors’ expression was estimated in all the patients on lung tissue by immunohistochemistry (IHC) and FACS analyses. SUVmax on PET, Intensity score on IHC and Mean fluorescence Index (MFI) on FACS analyses were measured. Results 75/94 (79.8%) cases had NSCLC, 14 (14.9%) had SCLC and 5 (5.3%) had lung NETs. All LC types showed increased CXCR4 expression on PET (SUVmax) and FACS (MFI). However, both these parameters (mean SUVmax = 10.30 ± 5.0; mean MFI = 349.0 ± 99.0) were significantly (p = 0.005) higher in SCLC as compared to NSCLC and lung NETs. PET SUVmax in adenocarcinoma (n = 16) were 8.00 ± 1.9 which was significantly (p = 0.003) higher than in squamous cell carcinoma (n = 54; 6.2 ± 2.15) and NOS (n = 5; 5.8 ± 1.5) subtypes of NSCLC. A significant correlation (r = 0.697; p = 001) was seen between SUVmax and MFI values in squamous cell NSCLC as well as in NSCLC-adenocarcinoma (r = 0.538, p = 0.031) which supports the specific uptake of 68Ga-Pentixafor by CXCR4 receptors. However, this correlation was not significant in SCLC (r = 0.435, p = 0.121) and NET (r = 0.747,p = 0.147) which may be due to the small sample size. 68Ga-Pentixafor PET/CT provided good sensitivity (85.7%) and specificity (78.1%) for differentiating SCLC from NSCLC (ROC cut-off SUVmax= 7.24). Almost similar sensitivity (87.5%) and specificity (71.4%) were observed (ROC cut-off SUVmax= 6.67) for differentiating adenocarcinoma and squamous cell variants of NSCLC. Conclusion Higher CXCR4 expression was seen in SCLC as compared to NSCLC and NETs on 68Ga-Pentixafor PET imaging. The findings may potentially supplement the existing data for inclusion and expanding CXCR4 -based radioligand therapies in LC beyond haematological malignancies.

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“…Expert panel statement I: CXCR4-directed molecular imaging may be useful for marginal zone lymphoma patients CXCR4-directed Molecular Imaging CXCR4 upregulation in varying tumour entities render it as an attractive target to identify cancerous tissue [5], which can be exploited using CXCR4-directed radiotracers, including the cyclic 68 Ga-labelled CXCR4-binding pentapeptide CPCR4.2 ([ 68 Ga]Ga-PentixaFor) [6]. Relative to the most widely used PET radiotracer 2-deoxy-2-[ 18 F]fuoro-D-glucose ([ 18 F]FDG), [ 68 Ga]Ga-PentixaFor often achieved equal, sometimes superior or at least complementary diagnostic performance in nuclear oncology [7,8,9,10]. Accordingly, [ 68 Ga]Ga-PentixaFor has been extensively tested to identify sites of disease in patients with solid tumours and haematological malignancies, providing promising results for marginal zone (MZL, ▶ Fig.…”

Section: Introductionmentioning

confidence: 99%

CXCR4-targeted Theranostics in Hematooncology: Opportunities and Challenges

Werner,

Haug,

Buske

et al. 2024

Nuklearmedizin

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C-X-C motif chemokine receptor 4 (CXCR4) is overexpressed in a multitude of cancers, including neoplasms of hematopoietic origin. This feature can be leveraged by a theranostic approach, which provides a read-out of the actual CXCR4 expression in vivo, followed by CXCR4-targeted radioligand therapy (RLT) exerting anti-cancer as well as myeloablative efficacy. In a recent meeting of hematooncology and nuclear medicine specialists, statements on the current clinical practice and future perspectives of this innovative concept were proposed and summarized in this opinion article. Experts concluded that i) CXCR4-directed [68Ga]Ga-PentixaFor PET/CT has the potential to improve imaging for patients with marginal zone lymphoma; ii) CXCR4-targeted RLT exerts anti-lymphoma efficacy and myeloablative effects in patients with advanced, treatment-refractory T-cell lymphomas; iii) prospective trials with CXCR4-based imaging and theranostics are warranted.

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Imaging CXCR4 receptors expression for staging multiple myeloma by using 68Ga-Pentixafor PET/CT: comparison with 18F-FDG PET/CT

Cited by 21 publications

References 37 publications

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

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

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

CXCR4-targeted Theranostics in Hematooncology: Opportunities and Challenges

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