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Overexpression of the chemokine-4 receptor (CXCR4) in brain tumors is associated with high cancer cell invasiveness. Recently, we reported the preclinical evaluation of  99m Tc-CXCR4-L (cyclo-D-Tyr-D-[NMe]Orn[EDDA- 99m Tc-6-hydrazinylnicotinyl]-Arg-NaI-Gly) as a SPECT radioligand capable of specifically detecting the CXCR4 protein. This research aimed to estimate the biokinetic behavior and radiation dosimetry of  99m Tc-CXCR4-L in healthy subjects, as well as to correlate the radiotracer uptake by brain tumors in patients, with the histological grade of differentiation and CXCR4 expression evaluated by immunohistochemistry.  99m Tc-CXCR4-L was obtained from freeze-dried kits prepared under GMP conditions (radiochemical purities >97%). Whole-body scans from six healthy volunteers were acquired at 0.3, 1, 2, 4, 6, and 24 h after  99m Tc-CXCR4-L administration (0.37 GBq). Time-activity curves of different source organs were obtained from the image sequence to adjust the biokinetic models. The OLINDA/EXM code was employed to calculate the equivalent and effective radiation doses. Nine patients with evidence of brain tumor injury (6 primaries and 3 recurrent), determined by MRI, underwent cerebral SPECT at 3 h after administration of  99m Tc-CXCR4-L (0.74 GBq). Data were expressed as a  T / B  (tumor uptake/background) ratio. Biopsy examinations included histological grading and anti-CXCR4 immunohistochemistry. Results showed a fast blood activity clearance ( T  1/2  α  = 0.81 min and  T  1/2  β  = 12.19 min) with renal and hepatobiliary elimination. The average equivalent doses were 6.10 E  − 04, 1.41 E  − 04, and 3.13 E  − 05 mSv/MBq for the intestine, liver, and kidney, respectively. The effective dose was 3.92 E  − 03 mSv/MBq. SPECT was positive in 7/9 patients diagnosed as grade II oligodendroglioma (two patients), grade IV glioblastoma (two patients), grade IV gliosarcoma (one patient), metastasis, and diffuse astrocytoma with  T / B  ratios of 1.3, 2.3, 13, 7, 19, 5.5, and 3.9, respectively, all of them with positive immunohistochemistry. A direct relationship between the grade of differentiation and the expression of CXCR4 was found. The two negative SPECT studies showed negative immunohistochemistry with a diagnosis of reactive gliosis. This “proof-of-concept” research warrants further clinical studies to establish the usefulness of  99m Tc-CXCR4-L in the diagnosis and prognosis of brain tumors.

contrast media and molecular imaging/contrast media and molecular imaging

<sup>99m</sup>Tc-CXCR4-L for Imaging of the Chemokine-4 Receptor Associated with Brain Tumor Invasiveness: Biokinetics, Radiation Dosimetry, and Proof of Concept in Humans

99mTc-CXCR4-L for Imaging of the Chemokine-4 Receptor Associated with Brain Tumor Invasiveness: Biokinetics, Radiation Dosimetry, and Proof of Concept in Humans

^99mTc-CXCR4-L for Imaging of the Chemokine-4 Receptor Associated with Brain Tumor Invasiveness: Biokinetics, Radiation Dosimetry, and Proof of Concept in Humans