[¹²⁴I]CLR1404 PET/CT in High-Grade Primary and Metastatic Brain Tumors

There is a continuous search for imaging techniques with high sensitivity and specificity for brain tumors. Positron emission tomography (PET) imaging has shown promise, though many PET agents either have a low tumor specificity or impractical physical half-lives. [¹²⁴I]CLR1404 is a small molecule alkylphosphocholine analogue that is thought to bind to plasma membrane lipid rafts and has shown high tumor-to-background ratios (TBR) in a previous pilot study in brain tumor patients. This study attempts to define the clinical value of [¹²⁴I]CLR1404 PET/CT (aka CLR124).

Adult patients with new or suspected recurrence of high-grade primary or metastatic brain tumors (N = 27) were injected with [¹²⁴I]CLR1404 followed by PET/CT at 6, 24, and 48 h. Standard uptake values (SUV) and TBR values were calculated for all time points. Uptake of [¹²⁴I]CLR1404 was qualitatively assessed, compared with magnetic resonance imaging (MRI), and correlated with clinical outcome. Final diagnosis (N = 25) was established based on surgically resected tissue or long-term follow-up.

Positive uptake with high TBR was detected in all but one patient with a final diagnosis of primary/recurrent brain tumor (12/13) and in less than half of patients with treatment-related changes (5/12). Concordance between [¹²⁴I]CLR1404 uptake and contrast enhancement on MRI was seen in < 40 %, with no concordance between T₂-hyperintensities and uptake. No significant difference in overall outcome was found between patients with and without [¹²⁴I]CLR1404 uptake.

The uptake pattern in these patients suggests a very high sensitivity of [¹²⁴I]CLR1404 PET/CT for diagnosing tumor tissue; however, tumor specificity needs to be further defined. Relative lack of concordance with standard MRI characteristics suggests that [¹²⁴I]CLR1404 PET/CT provides additional information about brain tumors compared to MRI alone, potentially improving clinical decision-making.