Clinical Applications of FDG PET and PET/CT in Head and Neck Cancer

18F-FDG PET plays an increasing role in diagnosis and management planning of head and neck cancer. Hybrid PET/CT has promoted the field of molecular imaging in head and neck cancer. This modality is particular relevant in the head and neck region, given the complex anatomy and variable physiologic FDG uptake patterns. The vast majority of 18F-FDG PET and PET/CT applications in head and neck cancer related to head and neck squamous cell carcinoma. Clinical applications of 18F-FDG PET and PET/CT in head and neck cancer include diagnosis of distant metastases, identification of synchronous 2nd primaries, detection of carcinoma of unknown primary and detection of residual or recurrent disease. Emerging applications are precise delineation of the tumor volume for radiation treatment planning, monitoring treatment, and providing prognostic information. The clinical role of 18F-FDG PET/CT in N0 disease is limited which is in line with findings of other imaging modalities. MRI is usually used for T staging with an intense discussion concerning the preferable imaging modality for regional lymph node staging as PET/CT, MRI, and multi-slice spiral CT are all improving rapidly. Is this review, we summarize recent literature on 18F-FDG PET and PET/CT imaging of head and neck cancer

Blocking Autophagy in Cancer-Associated Fibroblasts Supports Chemotherapy of Pancreatic Cancer Cells

In this study we evaluated the interaction of pancreatic cancer cells, cancer-associated fibroblasts, and distinct drugs such as α-cyano-4-hydroxycinnamate, metformin, and gemcitabine. We observed that α-cyano-4-hydroxycinnamate as monotherapy or in combination with metformin could significantly induce collagen I deposition within the stromal reaction. Subsequently, we demonstrated that cancer-associated fibroblasts impaired the anti-proliferation efficacy of α-cyano-4-hydroxycinnamate, metformin and gemcitabine. Interestingly, inhibition of autophagy in these fibroblasts can augment the anti-proliferation effect of these chemotherapeutics in vitro and can reduce the tumor weight in a syngeneic pancreatic cancer model. These results suggest that inhibiting autophagy in cancer-associated fibroblasts may contribute to strategies targeting cancer

FDG-PET underscores the key role of the thalamus in frontotemporal lobar degeneration caused by C9ORF72 mutations

C9ORF72 mutations are the most common cause of familial frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). MRI studies have investigated structural changes in C9ORF72-associated FTLD (C9FTLD) and provided first insights about a prominent involvement of the thalamus and the cerebellum. Our multicenter, F-18-fluorodeoxyglucose positron-emission tomography study of 22 mutation carriers with FTLD, 22 matched non-carriers with FTLD, and 23 cognitively healthy controls provided valuable insights into functional changes in C9FTLD: compared to non-carriers, mutation carriers showed a significant reduction of glucose metabolism in both thalami, underscoring the key role of the thalamus in C9FTLD. Thalamic metabolism did not correlate with disease severity, duration of disease, or the presence of psychotic symptoms. Against our expectations we could not demonstrate a cerebellar hypometabolism in carriers or non-carriers. Future imaging and neuropathological studies in large patient cohorts are required to further elucidate the central role of the thalamus in C9FTLD

Increased choline uptake in macrophages and prostate cancer cells does not allow for differentiation between benign and malignant prostate pathologies

Introduction: Inflammatory cells may contribute to the choline uptake in different prostate pathologies. The aim of this study was (i) to assess if inflammatory cells incorporate choline and (ii) to potentially detect differences compared to FDG uptake. Therefore we investigated the uptake of [H-3]choline and [F-18]FDG in human prostate carcinoma cells and human inflammatory cells. Methods: Macrophages were cultured from isolated mononuclear cells, gained by density gradient centrifugation of human buffy coats. T-lymphocytes, B-lymphocytes and granulocytes were enriched by density gradient centrifugation before cell sorting by means of flow cytometry was performed. [H-3]choline and [F-18]FDG uptake of isolated inflammatory cells as well as of LNCaP and PC-3 human prostate carcinoma cells was assessed simultaneously in dual tracer uptake experiments. Results: Macrophages showed highest [H-3]choline and [F-18]FDG uptake compared to the tracer uptake rates of leukocytes. [H-3]choline uptake of macrophages was in the same range as in prostate cancer cells. Lipopolysaccharide stimulation of macrophages resulted in an increase of [F-18]FDG uptake in macrophages, but not in an increased [H-3]choline uptake. Conclusions: The high [H-3]choline uptake in macrophages may be a source of false-positive PET results in diagnosis of prostate cancer by choline-PET/CT. As already known from FDG-PET, discrimination between tumor and inflammation in prostate cancer patients is not possible via choline-PET. Advances in knowledge and implications for patient care: The application of choline-PET for reliable primary prostate cancer detection and delineation has to be queried. (C) 2016 Elsevier Inc. All rights reserved

Early [18^{18}F]FET-PET in Gliomas after Surgical Resection: Comparison with MRI and Histopathology

Background The precise definition of the post-operative resection status in high-grade gliomas (HGG) is crucial for further management. We aimed to assess the feasibility of assessment of the resection status with early post-operative positron emission tomography (PET) using [$^{18}$F]O-(2-[$^{18}$F]-fluoroethyl)-L-tyrosine ([$^{18}$F]FET). Methods 25 patients with the suspicion of primary HGG were enrolled. All patients underwent preoperative [$^{18}$F]FET-PET and magnetic resonance imaging (MRI). Intra-operatively, resection status was assessed using 5-aminolevulinic acid (5-ALA). Imaging was repeated within 72h after neurosurgery. Post-operative [$^{18}$F]FET-PET was compared with MRI, intra-operative assessment and clinical follow-up. Results [$^{18}$F]FET-PET, MRI and intra-operative assessment consistently revealed complete resection in 12/25 (48%) patients and incomplete resection in 6/25 cases (24%). In 7 patients, PET revealed discordant findings. One patient was re-resected. 3/7 experienced tumor recurrence, 3/7 died shortly after brain surgery. Conclusion Early assessment of the resection status in HGG with [$^{18}$F]FET-PET seems to be feasible

Residual tumor tissue detected by [¹⁸F]FET-PET—Follow-up.

<p> Patient #18. <b>A,B:</b> sagittal slices. <b>C,D:</b> axial slices. <b>A:</b> Pre-operative PET showing focal uptake in the right parietal lobe. <b>B:</b> Suspicious uptake in the cranial border of the resection cavity 48h and <b>C:</b> 4 months after resection, consistent with vital tumor. <b>D:</b> Corresponding MRI 4 months after resection corroborating the PET finding.</p

Patients´ characteristics.

<p>Patients´ characteristics.</p

Residual glioma tissue detected by [¹⁸F]FET-PET–Re-resection.

<p>Patient #7. Transaxial slices of [¹⁸F]FET-PET (upper row) and corresponding contrast-enhanced T1-weighted MRI. <b>A:</b> Pre-operative PET with intense focal uptake in the left frontal lobe consistent with a lesion on MRI. <b>B:</b> Early postoperative PET with focal uptake at the cranio-medial border of the resection cavity, leading to re-resection; MRI displaying unspecific changes. <b>C:</b> Early postoperative PET after re-resection showing the resection cavity with no focal uptake in the border region, consistent with complete resection (confirmed by MRI). Histopathology confirmed glioblastoma.</p

Comparison of all 3 modalities: PET, MRI and intraoperative findings (IF).

<p><b>IR</b> = incomplete resection; <b>CR</b> = complete resection.</p><p>Comparison of all 3 modalities: PET, MRI and intraoperative findings (IF).</p