Advances in PET Imaging of the CXCR4 Receptor: [68Ga]Ga-PentixaFor

Abstract

[⁶⁸Ga]Ga-PentixaFor, a PET agent targeting CXCR4 is emerging as a versatile radiotracer with promising applications in oncology, cardiology and inflammatory disease. Preclinical work in various cancer cell lines have demonstrated high specificity and selectivity. In human investigations of several tumors, the most promising applications may be in multiple myeloma, certain lymphomas and myeloproliferative neoplasms. In the nononcologic setting, [⁶⁸Ga]Ga-PentixaFor could greatly improve detection for primary aldosteronism and other endocrine abnormalities. Similarly, atherosclerotic disease and other inflammatory conditions could also benefit from enhanced identification by CXCR4 targeting. Rapidly cleared from the body with a favorable imaging and radiation dosimetry profile that has been already studied in over 1000 patients, [⁶⁸Ga]Ga-PentixaFor is a worthy agent for further clinical exploration with potential for theranostic applications in hematologic malignancies.

Figure 1

Caption: Examples of several tumors exhibiting CXCR4 expression amenable to imaging with ⁶⁸Ga-PentixaFor This image was originally published in JNM and is used with permission. Buck AK, Haug A, Dreher N, Lambertini A, Higuchi T, Lapa C, Weich A, Pomper MG, Wester HJ, Zehndner A, Schirbel A, Samnick S, Hacker M, Pichler V, Hahner S, Fassnacht M, Einsele H, Serfling SE, Werner RA. Imaging of C-X-C Motif Chemokine Receptor 4 Expression in 690 Patients with Solid or Hematologic Neoplasms Using ⁶⁸Ga-Pentixafor PET. J Nucl Med. 2022 Nov;63(11):1687–1692.

Figure 2

Comparison of [¹⁸F]FDG uptake and CXCR4 expression. Display of two patients with Multiple Myeloma light chain kappa (MM LC κ) (patient #22) and MM IgG κ (patient #34), respectively. Both patients present with metabolically completely different forms of disease with patient 22 showing much greater activity with ⁶⁸Ga-PentixaFor and patient 34 showing the opposite. . MM= multiple myeloma; LC = light chain This image was originally published in Theranostics and is used with permission. Lapa C, Schreder M, Schirbel A, Samnick S, Kortüm KM, Herrmann K, Kropf S, Einsele H, Buck AK, Wester HJ, Knop S, Lückerath K. [⁶⁸Ga]Pentixafor-PET/CT for imaging of chemokine receptor CXCR4 expression in multiple myeloma - Comparison to [¹⁸F]FDG and laboratory values. Theranostics. 2017 Jan 1;7(1):205–212.

Figure 3

Performance of [⁶⁸Ga]Ga-PentixaFor PET/CT imaging in patients with adrenal cortical nodules. (First row) Right adrenal APA (2.9 cm in long diameter on CT imaging, arrow) with positive findings on PET/CT and PET scanning (SUV_max, 29.0; arrows) and strong expression of CXCR4. Patient was 34-y-old man with 5-y history of hypertension and 0.5-y history of hypokalemia (serum potassium, 2.9 mmol/L). (Second row) Pentixafor-avid CPA in left adrenal gland (SUV_max, 14.8; 1.9 cm in diameter on CT, arrows) in 36-y-old woman with Cushing syndrome. Strong expression of CXCR4 was observed on immunochemical staining. (Third row) Non–pentixafor-avid NFA in left adrenal gland (SUV_max, 3.8; 2.9 cm in long diameter on CT imaging, arrows) in 36-y-old man. This adenoma had no increases in CXCR4 expression. (Fourth row) Negative IAH lesion (1.5 cm in long diameter on CT imaging, arrow) in 46-y-old man on ⁶⁸Ga-pentixafor PET/CT and PET imaging (SUV_max, 4.3; arrow). No increased expression of CXCR4 was observed by immunochemical staining. APA= aldosterone producing adenoma; CPA= cortisol producing adenoma; NFA= nonfunctioning adrenal adenoma; IAH=idiopathic aldosterone hyperplasia This image was originally published in JNM. Ding J, Tong A, Zhang Y, Wen J, Zhang H, Hacker M, Huo L, Li X. Functional Characterization of Adrenocortical Masses in Nononcologic Patients Using 68Ga-Pentixafor. J Nucl Med. 2022 Mar;63(3):368-375. © SNMMI.