PET/CT imaging of the diapeutic alkylphosphocholine analog 124I-CLR1404 in high and low-grade brain tumors

Abstract

CLR1404 is a cancer-selective alkyl phosphocholine (APC) analog that can be radiolabeled with 124I for PET imaging, 131I for targeted radiotherapy and/or SPECT imaging, or 125I for targeted radiotherapy. Studies have demonstrated avid CLR1404 uptake and prolonged retention in a broad spectrum of preclinical tumor models. The purpose of this pilot trial was to demonstrate avidity of 124I-CLR1404 in human brain tumors and develop a framework to evaluate this uptake for use in larger studies. 12 patients (8 men and 4 women; mean age of 43.9 ± 15.1 y; range 23-66 y) with 13 tumors were enrolled. Eleven patients had suspected tumor recurrence and 1 patient had a new diagnosis of high grade tumor. Patients were injected with 185 MBq ± 10% of 124I-CLR1404 followed by PET/CT imaging at 6-, 24-, and 48-hour. 124I-CLR1404 PET uptake was assessed qualitatively and compared with MRI. After PET image segmentation SUV values and tumor to background ratios were calculated. There was no significant uptake of 124I-CLR1404 in normal brain. In tumors, uptake tended to increase to 48 hours. Positive uptake was detected in 9 of 13 lesions: 5/5 high grade tumors, 1/2 low grade tumors, 1/1 meningioma, and 2/4 patients with treatment related changes. 124I-CLR1404 uptake was not detected in 1/2 low grade tumors, 2/4 lesions from treatment related changes, and 1/1 indeterminate lesion. For 6 malignant tumors, the average tumor to background ratios (TBR) were 9.32 ± 4.33 (range 3.46 to 15.42) at 24 hours and 10.04 ± 3.15 (range 5.17 to 13.17) at 48 hours. For 2 lesions from treatment related change, the average TBR were 5.05 ± 0.4 (range 4.76 to 5.33) at 24 hours and 4.88 ± 1.19 (range 4.04 to 5.72) at 48 hours. PET uptake had areas of both concordance and discordance compared with MRI. 124I-CLR1404 PET demonstrated avid tumor uptake in a variety of brain tumors with high tumor-to-background ratios. There were regions of concordance and discordance compared with MRI, which has potential clinical relevance. Expansion of these studies is required to determine the clinical significance of the 124I-CLR1404 PET findings.

Keywords: CLR1404; PET; alkyl phosphocholine analog; brain tumor; high grade brain tumor; low grade brain tumor; molecular imaging.

Conflict of interest statement

None.

Figures

Figure 1

Patient with newly diagnosed high grade tumor (WHO Grade 4 glioma). A: T1 contrast-enhanced coronal MRI demonstrating heterogeneous tumor enhancement. B: Corresponding 124I-CLR1404 coronal PET with intense uptake laterally, inferiorly and medially, minimal uptake superiorly and no uptake centrally. C: Corresponding fused PET/MRI, with PET uptake extending slightly beyond MRI enhancement, except superiorly.

Figure 2

Patient with recurrence of a high grade tumor (WHO Grade 4 glioma) after prior treatments. A: Sagittal T1 contrast MRI demonstrates tumor enhancement adjacent to the anterior (open arrow) and posterior (closed arrow) margins of a resection cavity. B: 124I-CLR1404 sagittal PET demonstrates concordant uptake in the anterior enhancing tumor but no uptake in the posterior enhancing tumor. C: Fused PET/MRI image.

Figure 3

Patient with recurrence of a high grade tumor (WHO Grade 4 glioma). A: Axial T1 contrast MRI demonstrates 2 separate foci of tumor enhancement. B: 124I-CLR1404 axial PET demonstrates concordant uptake in the medial enhancing tumor (open arrow) but no significant uptake in the lateral enhancing tumor (closed arrow). C: Fused PET/MRI image further depicts these findings.

Figure 4

Patient with recurrent low grade tumor (WHO Grade 2 glioma). A: Axial T1 contrast MRI demonstrates a prior resection cavity in the anterior left temporal lobe but no enhancement. B: 124I-CLR1404 axial PET demonstrates mild uptake adjacent to the posterior resection cavity without enhancement on MRI. C: Fused PET/MRI image further depicts these findings.

Figure 5

Patient with suspected recurrent high grade tumor (WHO Grade 3 glioma) that was subsequently proven to represent treatment related changes. A: Axial T1 contrast MRI demonstrates 2 prior resection cavities with a small enhancing nodule (closed arrow) posterior to the larger cavity and a larger area of low signal intensity on T1 and high signal intensity on T2 (not shown). B: 124I-CLR1404 axial PET demonstrates no uptake in neither the enhancing nodule nor the high T2 signal. C: Fused PET/MRI image further depicts these findings.