¹⁸F-FET PET Uptake Characteristics in Patients with Newly Diagnosed and Untreated Brain Metastasis

Abstract

In patients with brain metastasis, PET using labeled amino acids has gained clinical importance, mainly regarding the differentiation of viable tumor tissue from treatment-related effects. However, there is still limited knowledge concerning the uptake characteristics in patients with newly diagnosed and untreated brain metastases. Hence, we evaluated the uptake characteristics in these patients using dynamic . In 39 of 45 brain metastases eligible for dynamic analysis, a wide range of TTP min was observed (median, 22.5 min; range, 4.5-47.5 min). All 18 F-FETnegative metastases had a diameter of # 1.0 cm, whereas metastases with a . 1.0 cm diameter all showed pathologic 18 F-FET uptake, which did not correlate with lesion size. The highest variability of uptake intensity was observed within the group of melanoma metastases. Conclusion: Untreated metastases predominantly show increased 18 F-FET uptake, and only a third of metastases , 1.0 cm were 18 F-FET-negative, most likely because of scanner resolution and partial-volume effects. In metastases . 1.0 cm, 18 F-FET uptake intensity was highly variable and independent of tumor size (even intraindividually). 18 F-FET PET might provide additional information beyond the tumor extent by reflecting molecular features of a metastasis and might be a useful tool for future clinical applications, for example, response assessment. Br ain metastases are secondary intracerebral neoplasms and occur in up to 17% of all cancer patients. Because of the improved treatment options for extracranial primary tumors with consecutive prolonged survival, the incidence of brain metastases is expected to increase. The most common originating primary tumors are lung cancer, breast cancer, and malignant melanoma (in sum up to 80% of all metastases) (1).Systemic treatment usually consists of chemotherapy, immunotherapies, and targeted therapy, which, however, are mostly unable to cross the blood-brain barrier (BBB) (2,3). In brain metastases, treatment options such as whole resection, whole-brain radiation therapy, external fractionated radiotherapy, radiosurgery, and brachytherapy (4,5) are frequently used; additionally, recent experimental developments are heading toward new immunotherapies being able to cross the BBB (6).Currently, contrast-enhanced standard MRI represents the diagnostic gold standard in the clinical management of patients with brain metastases (7). However, the diagnostic performance of this technique is limited regarding the differentiation between primary and secondary intracerebral malignancies, tumor delineation, differentiation of recurrent brain metastasis from posttherapeutic effects, and providing prognostic information in newly diagnosed brain tumors (8,9). Thus, there is an increasing demand for additional imaging options.Regarding the diagnostic evaluation of intracerebral neoplasms, molecular imaging using PET has gained great importance. Particularly, radiolabeled amino acids such as O-(2-18 F-fluoroethyl)-L-tyrosine ( 18 F-FET) were reported to be particula...

Biomarkers for Clinical Benefit of Immune Checkpoint Inhibitor Treatment—A Review From the Melanoma Perspective and Beyond

“…Further clinical evaluation of FLT-PET in ICI is, therefore, warranted. O-(2-[18F]fluoroethyl)- l -tyrosine (FET-)PET can be used to specifically image primary brain tumors and metastases to the brain which can be differentiated from healthy, inflamed, and radionecrotic tissue ( 173 , 174 ). FET-uptake correlates with ki-67 expression and could be a potential biomarker for early response assessment ( 175 ).…”

Brain metastases: neuroimaging

“…For instance, in a large study ( n = 393 patients) using FET, normalized standardized uptake value of HGG and nonglial tumors were not dissimilar (1.99 ± 0.74 and 2.09 ± 0.62, median ± sd , respectively) (Hutterer et al, 2013). Another limitation is that the sensitivity of FET PET for small metastases (< 1.0 cm) is low (Unterrainer et al, 2017). …”

Evaluation of the Performance of 18F-Fluorothymidine Positron Emission Tomography/Computed Tomography (18F-FLT-PET/CT) in Metastatic Brain Lesions

“…Generally, SUVmax has been found to correlate with tumors’ aggressiveness and response to treatments, while SUVmax thresholds have been used for discriminating between benign from malignant diseases, and in the case of gliomas, between low and high grades. Because of low SUVmax values for 18F-FLT brain PET measurements, we also used T/B and other SUV values and proliferative volumes for our analysis [20,21,22,23,24]. To our knowledge, this is the first study with such an approach for metastatic brain lesions with 18F-FLT.…”