Simultaneously acquired PET and ASL imaging biomarkers may be helpful in differentiating progression from pseudo-progression in treated gliomas.

OBJECTIVES: The aim of this work was investigating the methods based on coupling cerebral perfusion (ASL) and amino acid metabolism ([18F]DOPA-PET) measurements to evaluate the diagnostic performance of PET/MRI in glioma follow-up. METHODS: Images were acquired using a 3-T PET/MR system, on a prospective cohort of patients addressed for possible glioma progression. Data were preprocessed with statistical parametric mapping (SPM), including registration on T1-weighted images, spatial and intensity normalization, and tumor segmentation. As index tests, tumor isocontour maps of [18F]DOPA-PET and ASL T-maps were created and metabolic/perfusion abnormalities were evaluated with the asymmetry index z-score. SPM map analysis of significant size clusters and semi-quantitative PET and ASL map evaluation were performed and compared to the gold standard diagnosis. Lastly, ASL and PET topography of significant clusters was compared to that of the initial tumor. RESULTS: Fifty-eight patients with unilateral treated glioma were included (34 progressions and 24 pseudo-progressions). The tumor isocontour maps and T-maps showed the highest specificity (100%) and sensitivity (94.1%) for ASL and [18F]DOPA analysis, respectively. The sensitivity of qualitative SPM maps and semi-quantitative rCBF and rSUV analyses were the highest for glioblastoma. CONCLUSION: Tumor isocontour T-maps and combined analysis of CBF and [18F]DOPA-PET uptake allow achieving high diagnostic performance in differentiating between progression and pseudo-progression in treated gliomas. The sensitivity is particularly high for glioblastomas. KEY POINTS: • Applied separately, MRI and PET imaging modalities may be insufficient to characterize the brain glioma post-therapeutic profile. • Combined ASL and [18F]DOPA-PET map analysis allows differentiating between tumor progression and pseudo-progression.

Diagnostic and prognostic value of 18F-FDG PET, CT, and MRI in perineural spread of head and neck malignancies.

OBJECTIVES: We assessed whether quantitative imaging biomarkers derived from fluorodeoxyglucose-positron emission tomography (18F-FDG PET) could be extracted from perineural spread (PNS) in head and neck malignancies (HNM) to improve patient risk stratification. METHODS: A case-control exploratory study (1:2 ratio) enrolled 81 patients with FDG-avid HNM. The case-group comprised 28 patients with documented PNS (reference: expert consensus), including 14 squamous cell carcinomas (SCC). Imaging biomarkers were extracted from the PNS on 18F-FDG PET, CT-scan, and MRI. The control-group enrolled 53 SCCs. The Cox proportional-hazards regression model explored the association with overall survival by univariate and multivariate analyses. RESULTS: The rate of PNS detection by 18F-FDG PET was 100% in the case-group. Quantitative imaging biomarkers were not associated with the presence of sensory (p>0.20) or motor (p>0.10) symptoms. In SCC patients (case: 14; control: 53), PNS was associated with a hazard ratio of death of 5.5 (95%CI: 1.4:20.9) by multivariate analysis. Increased cranial nerve SUVmax was significantly associated with poorer overall survival by univariate analysis (p=0.001). CONCLUSIONS: Our pilot study showed the feasibility of extracting 18F-FDG PET biomarkers from PNS in FDG-avid HNM. Our results encourage the development of new PET/CT- or PET/MRI-guided management strategies in further prospective studies. KEY POINTS: • 18F-FDG PET/CT detects PNS in FDG-avid HNM. • PNS metabolism is more heterogeneous than healthy tissue. • PNS diagnosis is crucial: most patients were asymptomatic, N0 and M0. • PNS diagnosis is associated with poorer overall survival in SCC. • PET/CT- or PET/MRI-guided management strategies should be evaluated.

[68Ga]RGD Versus [18F]FDG PET Imaging in Monitoring Treatment Response of a Mouse Model of Human Glioblastoma Tumor with Bevacizumab and/or Temozolomide.

PURPOSE: The aim of this study was to evaluate positron emission tomography (PET) imaging with [68Ga]NODAGA-c(RGDfK) ([68Ga]RGD), in comparison with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), for early monitoring of the efficacy of an antiangiogenic agent associated or not with chemotherapy, in a mouse model of glioblastoma (GB). PROCEDURES: Mice bearing U87MG human GB cells line were parted into five groups of five mice each. One group was imaged at baseline before the treatment phase; another group was treated with bevacizumab (BVZ), another group with temozolomide (TMZ), another group with both agents, and the last one was the control group. Tumors growth and biological properties were evaluated by caliper measurements and PET imaging at three time points (baseline, during treatment t1 = 4-6 days and t2 = 10-12 days). At the end of the study, tumors were counted and analyzed by immunohistochemistry (CD31 to evaluate microvessel density). RESULTS: The tumor volume assessed by caliper measurements was significantly greater at t1 in the control group than in the TMZ + BVZ-treated group or in the BVZ-treated group. At t2, tumor volume of all treated groups was significantly smaller than that of the control group. [18F]FDG PET failed to reflect this efficacy of treatment. In contrast, at t1, the [68Ga]RGD tumor uptake was concordant with tumor growth in controls and in treated groups. At t2, a significant increase in tumor uptake of [68Ga]RGD vs. t1 was only observed in the TMZ-treated group, reflecting a lack of angiogenesis inhibition, whereas TMZ + BVZ resulted in a dramatic tumor arrest, reduction in microvessel density and stable tumor [68Ga]RGD uptake. CONCLUSIONS: [68Ga]RGD is a useful PET agent for in vivo angiogenesis imaging and can be useful for monitoring antiangiogenic treatment associated or not with chemotherapy.

Imaging-guided precision medicine in glioblastoma patients treated with immune checkpoint modulators: research trend and future directions in the field of imaging biomarkers and artificial intelligence.

Immunotherapies that employ immune checkpoint modulators (ICMs) have emerged as an effective treatment for a variety of solid cancers, as well as a paradigm shift in the treatment of cancers. Despite this breakthrough, the median survival time of glioblastoma patients has remained at about 2 years. Therefore, the safety and anti-cancer efficacy of combination therapies that include ICMs are being actively investigated. Because of the distinct mechanisms of ICMs, which restore the immune system's anti-tumor capacity, unconventional immune-related phenomena are increasingly being reported in terms of tumor response and progression, as well as adverse events. Indeed, immunotherapy response assessments for neuro-oncology (iRANO) play a central role in guiding cancer patient management and define a "wait and see strategy" for patients treated with ICMs in monotherapy with progressive disease on MRI. This article deciphers emerging research trends to ameliorate four challenges unaddressed by the iRANO criteria: (1) patient selection, (2) identification of immune-related phenomena other than pseudoprogression (i.e., hyperprogression, the abscopal effect, immune-related adverse events), (3) response assessment in combination therapies including ICM, and (4) alternatives to MRI. To this end, our article provides a structured approach for standardized selection and reporting of imaging modalities to enable the use of precision medicine by deciphering the characteristics of the tumor and its immune environment. Emerging preclinical or clinical innovations are also discussed as future directions such as immune-specific targeting and implementation of artificial intelligence algorithms.

99mTc-HMPAO-leukocyte scintigraphy for diagnosis and therapy monitoring of skull base osteomyelitis.

OBJECTIVE: Skull base osteomyelitis (SBO) is a rare but life-threatening disease observed in elderly diabetic patients, with high risk of recurrence and difficult therapeutic management. The diagnosis is ascertained from a set of clinical, biological, and imaging findings. CT and MRI allow initial diagnosis, but are not accurate to affirm healing at the end of therapy. 99mTc-HMPAO-Leucocyte Scintigraphy (LS) is highly sensitive and specific for the detection of infection. The aim of this study was to evaluate LS i) for initial diagnosis, and ii) to confirm healing at the end of antibiotherapy in SBO. STUDY DESIGN: We retrospectively reviewed from November 2011 to September 2015 all patients with confirmed SBO who underwent LS twice, at diagnosis and at the end of antibiotic therapy in our nuclear medicine department (n = 27). METHODS: Clinical, biological, CT, LS, and follow-up data were recorded in all patients. LS images (planar and tomographic performed 4 hours and 24 hours after intravenous injection of autologous Tc-99m-HMPAO-leucocytes) were visually assessed and quantified. RESULTS: At initial diagnosis, 25 of 27 patients had a positive LS. At the end of antibiotic therapy (3 ± 1 months duration), 26 of 27 patients had a negative LS. During subsequent follow-up (= or >6 months), the disease recurred in four patients including three with a negative postantibiotherapy LS scan. CONCLUSION: In this retrospective study, LS was powerful for initial diagnostic of SBO and for healing assessment at the end of antibiotic therapy. We conclude it is a useful technique for therapeutic monitoring of SBO. LEVEL OF EVIDENCE: 4.

Comparison and evaluation of two RGD peptides labelled with 68Ga or 18F for PET imaging of angiogenesis in animal models of human glioblastoma or lung carcinoma.

The aim of this study was to evaluate two RGD radiotracers radiolabelled with fluorine-18 or gallium-68, in detecting angiogenesis in grafted human tumours and monitoring their treatment with the anti-angiogenic agent bevacizumab. Sixteen mice bearing an U87MG tumour in one flank and a contralateral A549 tumour were treated with intravenous injections of bevacizumab twice a week for 3 weeks. PET images with 18F-RGD-K5 and 68Ga-RGD were acquired before treatment (baseline), after three bevacizumab injections (t1) and after seven bevacizumab injections (t2). In A549 tumours, the treatment stopped the tumour growth, with a tumour volume measured by calliper remaining between 0.28 and 0.40 cm3. The decrease in tumour uptake of both RGD tracers was non-significant. Therefore it was not possible to predict this efficacy on tumour growth based on RGD PET results, whereas ex vivo measurements showed a significantly lower tumour uptake of both tracers in mice sacrificed at t2 vs. at baseline. In U87MG tumours, the uptake measured on PET decreased during treatment, reflecting the partial therapeutic effect observed on tumour volume, consisting in a decrease in the slope of tumour growth. Using 18F-RGD-K5, this decrease in tumour SUVmax became significant at t1, whereas it was also observed with the 68Ga-RGD tracer, but only at t2. 18F-RGD-K5 appeared more efficient than 68Ga-RGD in the visualisation and follow-up of U87MG tumours. The comparison of those results with those of immunohistochemistry at baseline and at t2 favoured the hypothesis that tumour RGD uptake reflects other cancer properties than just its angiogenic capacity.