PET/CT and SPECT/CT Imaging of HER2-Positive Breast Cancer.

HER2 (Human Epidermal Growth Factor Receptor 2)-positive breast cancer is characterized by amplification of the HER2 gene and is associated with more aggressive tumor growth, increased risk of metastasis, and poorer prognosis when compared to other subtypes of breast cancer. HER2 expression is therefore a critical tumor feature that can be used to diagnose and treat breast cancer. Moving forward, advances in HER2 in vivo imaging, involving the use of techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), may allow for a greater role for HER2 status in guiding the management of breast cancer patients. This will apply both to patients who are HER2-positive and those who have limited-to-minimal immunohistochemical HER2 expression (HER2-low), with imaging ultimately helping clinicians determine the size and location of tumors. Additionally, PET and SPECT could help evaluate effectiveness of HER2-targeted therapies, such as trastuzumab or pertuzumab for HER2-positive cancers, and specially modified antibody drug conjugates (ADC), such as trastuzumab-deruxtecan, for HER2-low variants. This review will explore the current and future role of HER2 imaging in personalizing the care of patients diagnosed with breast cancer.

Advances in PET/CT Imaging for Breast Cancer.

One out of eight women will be affected by breast cancer during her lifetime. Imaging plays a key role in breast cancer detection and management, providing physicians with information about tumor location, heterogeneity, and dissemination. In this review, we describe the latest advances in PET/CT imaging of breast cancer, including novel applications of 18F-FDG PET/CT and the development and testing of new agents for primary and metastatic breast tumor imaging and therapy. Ultimately, these radiopharmaceuticals may guide personalized approaches to optimize treatment based on the patient's specific tumor profile, and may become a new standard of care. In addition, they may enhance the assessment of treatment efficacy and lead to improved outcomes for patients with a breast cancer diagnosis.

PET Imaging in Bladder Cancer: An Update and Future Direction.

Molecular imaging with positron emission tomography is a powerful tool in bladder cancer management. In this review, we aim to address the current place of the PET imaging in bladder cancer care and offer perspectives on potential future radiopharmaceutical and technological advancements. A special focus is given to the following: the role of [18F] 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography in the clinical management of bladder cancer patients, especially for staging and follow-up; treatment guided by [18F]FDG PET/CT; the role of [18F]FDG PET/MRI, the other PET radiopharmaceuticals beyond [18F]FDG, such as [68Ga]- or [18F]-labeled fibroblast activation protein inhibitor; and the application of artificial intelligence.

Advances in PET/CT Imaging for Breast Cancer Patients and Beyond.

Breast cancer is the most common cancer in women around the world and the fifth leading cause of cancer-related death [...].

Emerging and Evolving Concepts in Cancer Immunotherapy Imaging.

Criteria based on measurements of lesion diameter at CT have guided treatment with historical therapies due to the strong association between tumor size and survival. Clinical experience with immune checkpoint modulators shows that editing immune system function can be effective in various solid tumors. Equally, novel immune-related phenomena accompany this novel therapeutic paradigm. These effects of immunotherapy challenge the association of tumor size with response or progression and include risks and adverse events that present new demands for imaging to guide treatment decisions. Emerging and evolving approaches to immunotherapy highlight further key issues for imaging evaluation, such as dissociated response following local administration of immune checkpoint modulators, pseudoprogression due to immune infiltration in the tumor environment, and premature death due to hyperprogression. Research that may offer tools for radiologists to meet these challenges is reviewed. Different modalities are discussed, including immuno-PET, as well as new applications of CT, MRI, and fluorodeoxyglucose PET, such as radiomics and imaging of hematopoietic tissues or anthropometric characteristics. Multilevel integration of imaging and other biomarkers may improve clinical guidance for immunotherapies and provide theranostic opportunities.

A machine-learning-based combination of criteria to detect bladder cancer lymph node metastasis on [18F]FDG PET/CT: a pathology-controlled study.

OBJECTIVES: Initial pelvic lymph node (LN) staging is pivotal for treatment planification in patients with muscle-invasive bladder cancer (MIBC), but [18F]FDG PET/CT provides insufficient and variable diagnostic performance. We aimed to develop and validate a machine-learning-based combination of criteria on [18F]FDG PET/CT to accurately identify pelvic LN involvement in bladder cancer patients. METHODS: Consecutive patients with localized MIBC who performed preoperative [18F]FDG PET/CT between 2010 and 2017 were retrospectively assigned to training (n = 129) and validation (n = 44) sets. The reference standard was the pathological status after extended pelvic LN dissection. In the training set, a random forest algorithm identified the combination of criteria that best predicted LN status. The diagnostic performances (AUC) and interrater agreement of this combination of criteria were compared to a consensus of experts. RESULTS: The overall prevalence of pelvic LN involvement was 24% (n = 41/173). In the training set, the top 3 features were derived from pelvic LNs (SUVmax of the most intense LN, and product of diameters of the largest LN) and primary bladder tumor (product of diameters). In the validation set, diagnostic performance did not differ significantly between the combination of criteria (AUC = 0.59 95%CI [0.43-0.73]) and the consensus of experts (AUC = 0.64 95%CI [0.48-0.78], p = 0.54). The interrater agreement was equally good with Κ = 0.66 for both. CONCLUSION: The developed machine-learning-based combination of criteria performs as well as a consensus of experts to detect pelvic LN involvement on [18F]FDG PET/CT in patients with MIBC. KEY POINTS: • The developed machine-learning-based combination of criteria performs as well as experts to detect pelvic LN involvement on [18F]FDG PET/CT in patients with muscle-invasive bladder cancer. • The top 3 features to predict LN involvement were the SUVmax of the most intense LN, the product of diameters of the largest LN, and the product of diameters of the primary bladder tumor.

Delayed [ 18 F]-FDG PET Imaging Increases Diagnostic Performance and Reproducibility to Differentiate Recurrence of Brain Metastases From Radionecrosis.

PURPOSE: Differentiating brain metastasis recurrence from radiation necrosis can be challenging during MRI follow-up after stereotactic radiotherapy. [ 18 F]-FDG is the most available PET tracer, but standard images performed 30 to 60 minutes postinjection provide insufficient accuracy. We compared the diagnostic performance and interobserver agreement of [ 18 F]-FDG PET with delayed images (4-5 hours postinjection) with the ones provided by standard and dual-time-point imaging. METHODS: Consecutive patients referred for brain [ 18 F]-FDG PET after inconclusive MRI were retrospectively included between 2015 and 2020 in 3 centers. Two independent nuclear medicine physicians interpreted standard (visually), delayed (visually), and dual-time-point (semiquantitatively) images, respectively. Adjudication was applied in case of discrepancy. The final diagnosis was confirmed histologically or after 6 months of MRI follow-up. Areas under the receiver operating characteristic curves were pairwise compared. RESULTS: Forty-eight lesions from 46 patients were analyzed. Primary tumors were mostly located in the lungs (57%) and breast (23%). The median delay between radiotherapy and PET was 15.7 months. The final diagnosis was tumor recurrence in 24 of 48 lesions (50%), with histological confirmation in 19 of 48 lesions (40%). Delayed images provided a larger area under the receiver operating characteristic curve (0.88; 95% confidence interval [CI], 0.75-0.95) than both standard (0.69; 95% CI, 0.54-0.81; P = 0.0014) and dual-time-point imaging (0.77; 95% CI, 0.63-0.88; P = 0.045), respectively. Interobserver agreement was almost perfect with delayed images ( κ = 0.83), whereas it was moderate with both standard ( κ = 0.48) and dual-time-point images ( κ = 0.61). CONCLUSIONS: [ 18 F]-FDG PET with delayed images is an accurate and reliable alternative to differentiate metastasis recurrence from radiation necrosis in case of inconclusive MRI after brain stereotactic radiotherapy.

What Does PET Imaging Bring to Neuro-Oncology in 2022? A Review.

PET imaging is being increasingly used to supplement MRI in the clinical management of brain tumors. The main radiotracers implemented in clinical practice include [18F]FDG, radiolabeled amino acids ([11C]MET, [18F]FDOPA, [18F]FET) and [68Ga]Ga-DOTA-SSTR, targeting glucose metabolism, L-amino-acid transport and somatostatin receptors expression, respectively. This review aims at addressing the current place and perspectives of brain PET imaging for patients who suffer from primary or secondary brain tumors, at diagnosis and during follow-up. A special focus is given to the following: radiolabeled amino acids PET imaging for tumor characterization and follow-up in gliomas; the role of amino acid PET and [18F]FDG PET for detecting brain metastases recurrence; [68Ga]Ga-DOTA-SSTR PET for guiding treatment in meningioma and particularly before targeted radiotherapy.

Impact of point-spread function reconstruction on dynamic and static 18F-DOPA PET/CT quantitative parameters in glioma.

BACKGROUND: Quantification of dynamic and static parameters extracted from 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-DOPA, FDOPA) positron emission tomography (PET)/computed tomography (CT) plays a critical role for glioma assessment. The objective of the present study was to investigate the impact of point-spread function (PSF) reconstruction on these quantitative parameters. METHODS: Fourteen patients with untreated gliomas and investigated with FDOPA PET/CT were analyzed. The distribution of the 14 cases was as follows: 6 astrocytomas-isocitrate dehydrogenase-mutant; 2 oligodendrogliomas/1p19q-codeleted-isocitrate dehydrogenase-mutant; and 6 isocitrate dehydrogenase-wild-type glioblastomas. A 0-20-min dynamic images (8×15, 2×30, 2×60, and 3×300 s post-injection) and a 0-20-min static image were reconstructed with and without PSF. Tumoral volumes-of-interest were generated on all of the PET series and the background volumes-of-interest were generated on the 0-20-min static image with and without PSF. Static parameters (SUVmax and SUVmean) of the tumoral and the background volumes-of-interest and kinetic parameters (K1 and k2) of the tumoral volumes-of-interest extracted from using full kinetic analysis were provided. PSF and non-PSF quantitative parameters values were compared. RESULTS: Thirty-three tumor volumes-of-interest and 14 background volumes-of-interest were analyzed. PSF images provided higher tumor SUVmax than non-PSF images for 23/33 VOIs [median SUVmax =3.0 (range, 1.4-10.2) with PSF vs. 2.7 (range, 1.4-9.1) without PSF; P<0.001] and higher tumor SUVmean for 13/33 volumes-of-interest [median SUVmean =2.0 (range, 0.8-7.6) with PSF vs. 2.0 (range, 0.8-7.4) without PSF; P=0.002]. K1 and k2 were significantly lower with PSF than without PSF [respectively median K1 =0.077 mL/ccm/min (range, 0.043-0.445 mL/ccm/min) with PSF vs. 0.101 mL/ccm/min (range, 0.055-0.578 mL/ccm/min) without PSF; P<0.001 and median k2 =0.070 min-1 (range, 0.025-0.146 min-1) with PSF vs. 0.081 min-1 (range, 0.027-0.180 min-1) without PSF; P<0.001]. Background SUVmax and SUVmean were statistically unaffected [respectively median SUVmax =1.7 (range, 1.3-2.0) with PSF vs. 1.7 (range, 1.3-1.9) without PSF; P=0.346 and median SUVmean =1.5 (range, 1.0-1.8) with PSF vs. 1.5 (range, 1.0-1.7) without PSF; P=0.371]. CONCLUSIONS: The present study confirms that PSF significantly increases tumor activity concentrations measured on PET images. PSF algorithms for quantitative PET/CT analysis should be used with caution, especially for quantification of kinetic parameters.

Intracavernous Schwannoma Characterized With 18F-FDG, 68Ga-DOTATOC, and 18F-Choline PET.

ABSTRACT: We report the case of a 75-year-old man with history of prostate cancer whose left intracavernous lesion was successfully characterized by 3 PETs performed successively with different tracers. This poorly characterized tumor was initially discovered on an MRI conducted to investigate an acute diplopia and slowly growing during follow-up. On 18F-FDG PET, the lesion showed no significant uptake, and no extracranial lesion was found nor did it have increased 68Ga-DOTATOC uptake. Finally, this tumor displayed a high 18F-choline uptake, and no extracranial lesion was revealed with this tracer. The diagnosis of schwannoma without malignancy criterion was proven by biopsy.

Combining 18F-DOPA PET and MRI with perfusion-weighted imaging improves delineation of high-grade subregions in enhancing and non-enhancing gliomas prior treatment: a biopsy-controlled study.

PURPOSE: We aimed to compare spatial extent of high-grade subregions detected with combined [18F]-dihydroxyphenylalanine (18F-DOPA) PET and MRI to the one provided by advanced multimodal MRI alone including Contrast-enhanced (CE) and Perfusion weighted imaging (PWI). Then, we compared the accuracy between imaging modalities, in a per biopsy analysis. METHODS: Participants with suspected diffuse glioma were prospectively included between June 2018 and September 2019. Volumes of high-grade subregions were delineated respectively on 18F-DOPA PET and MRI (CE and PWI). Up to three per-surgical neuronavigation-guided biopsies were performed per patient. RESULTS: Thirty-eight biopsy samples from sixteen participants were analyzed. Six participants (38%) had grade IV IDH wild-type glioblastoma, six (38%) had grade III IDH-mutated astrocytoma and four (24%) had grade II IDH-mutated gliomas. Three patients had intratumoral heterogeneity with coexisting high- and low-grade tumor subregions. High-grade volumes determined with combined 18F-DOPA PET/MRI (median of 1.7 [interquartile range (IQR) 0.0, 19.1] mL) were larger than with multimodal MRI alone (median 1.3 [IQR 0.0, 12.8] mL) with low overlap (median Dice's coefficient 0.24 [IQR 0.08, 0.59]). Delineation volumes were substantially increased in five (31%) patients. In a per biopsy analysis, combined 18F-DOPA PET/MRI detected high-grade subregions with an accuracy of 58% compared to 42% (p = 0.03) with CE MRI alone and 50% (p = 0.25) using multimodal MRI (CE + PWI). CONCLUSIONS: The addition of 18F-DOPA PET to multimodal MRI (CE and PWI) enlarged the delineation volumes and enhanced overall accuracy for detection of high-grade subregions. Thus, combining 18F-DOPA with advanced MRI may improve treatment planning in newly diagnosed gliomas.

Additive Value of Dynamic FDOPA PET/CT for Glioma Grading.

Purpose: The aim of this study was to assess the value of the FDOPA PET kinetic parameters extracted using full kinetic analysis for tumor grading with neuronavigation-guided biopsies as reference in patients with newly-diagnosed gliomas. Methods: Fourteen patients with untreated gliomas were investigated. Twenty minutes of dynamic positron-emission tomography (PET) imaging and a 20-min static image 10 min after injection were reconstructed from a 40-min list-mode acquisition immediately after FDOPA injection. Tumors volume-of-interest (VOI) were generated based on the MRI-guided brain biopsies. Static parameters (TBRmax and TBRmean) and kinetic parameters [K1 and k2 using full kinetic analysis with the reversible single-tissue compartment model with blood volume parameter and the time-to-peak (TTP)] were extracted. Performances of each parameter for differentiating low-grade gliomas (LGG) from high-grade gliomas (HGG) were evaluated by receiver-operating characteristic analyses (area under the curve; AUC). Results: Thirty-two tumoral VOI were analyzed. K1, k2, and TTP were significantly higher for HGG than for LGG (median K1-value = 0.124 vs. 0.074 ml/ccm/min, p = 0.025, median k2-value = 0.093 vs. 0.063 min-1, p = 0.025, and median TTP-value = 10.0 vs. 15.0 min, p = 0.025). No significant difference was observed for the static parameters. The AUC for the kinetic parameters was higher than the AUC for the static parameters (respectively, AUCK1 = 0.787, AUCk2 = 0.785, AUCTTP = 0.775, AUCTBRmax = 0.551, AUCTBRmean = 0.575), significantly compared to TBRmax (respectively, p = 0.001 for K1, p = 0.031 for k2, and p = 0.029 for TTP). Conclusion: The present study suggests an additive value of FDOPA PET/CT kinetic parameters for newly-diagnosed gliomas grading.

The Added Value of Bloodpool SPECT/CT in Painful Non-Operated Foot and Ankle Undiagnosed With Standard Three-Phase Bone Scintigraphy.

Purpose: To evaluate the interest of adding a bloodpool SPECT/CT to standard three-phase bone scintigraphy (BS) for etiological diagnosis of subacute and chronic lower extremity pains. Methods: We prospectively included patients addressed for pain of lower extremities lasting for at least 6 weeks, without previous surgery. They underwent a standard three-phase BS including late phase SPECT/CT, modified with an additional bloodpool SPECT/CT acquisition. Two independent physicians interpreted the images provided by both protocols. Diagnostic conclusion, diagnostic confidence, and interrater agreements were compared. Results: One hundred and eighteen lower extremities from 113 patients were analyzed (71 men, median age of 53 years). Adding bloodpool SPECT/CT to standard three-phase BS changed diagnostic conclusions in 24.6% (29/118) of lower extremities. The modified protocol revealed at least one diagnostic conclusion explaining the pain in 89% of extremities, rather than 83.1% with the standard protocol (p = 0.02). Tendinopathies were diagnosed in 12.7% of lower extremities, rather than 4.2% with standard BS (p = 0.002). Adding bloodpool SPECT/CT substantially increased overall confidence of each reader (p < 0.001). Inter-reader agreement was not significantly impacted. Conclusion: Adding bloodpool SPECT/CT to standard three-phase BS impacted diagnostic conclusion in a quarter of the patients with painful lower extremities, notably by revealing significantly more tendonitis.

Deep brain stimulation of the internal globus pallidus does not affect the limbic circuit in patients with Parkinson's disease: a PET study.

INTRODUCTION: Internal globus pallidus (GPi) deep brain stimulation (DBS) is a safe and effective alternative treatment in Parkinson's disease (PD) for patients with cognitive impairment. However, no study has yet investigated metabolic changes within a large series of patients undergoing GPi stimulation. OBJECTIVE: We assessed motor, cognitive and psychiatric changes, as well as modifications in brain glucose metabolism measured with FDG-PET, before and after bilateral GPi-DBS. METHODS: In the same week, 32 patients with PD underwent a motor, cognitive and psychiatric assessment and a resting-state FDG-PET scan, 4 months before and 4 months after GPi-DBS surgery. For the voxelwise metabolic change assessment, the p value was controlled for multiple comparisons using the family wise error rate. RESULTS: After GPi-DBS surgery, patients showed a significant overall improvement in motor status. No cognitive or psychiatric changes were observed after surgery. Nor were any clusters with significantly relative metabolic changes found in the limbic circuit after surgery. Clusters with significantly relative metabolic changes were observed in the left and right Brodmann area (BA) 6, the right BA 9, the right and left BA 39 and the left BA 17. CONCLUSION: The present study confirmed that GPi-DBS is an effective treatment in patients with advanced PD, owing to metabolic changes in the areas involved in motor execution. The absence of relative metabolic decrease in the limbic circuit and the few changes affecting the associative circuit could explain why GPi-DBS is cognitively safe.

Increased thyroid uptake on 18F-FDG PET/CT is associated with the development of permanent hypothyroidism in stage IV melanoma patients treated with anti-PD-1 antibodies.

PURPOSE: To determine performances of 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography (PET) to detect the development of permanent thyroid dysfunction (PTD), and to evaluate the prognostic value of early increased thyroid uptake in stage IV melanoma patients treated with anti-programmed death 1 (anti-PD-1) antibodies. METHODS: Twenty-nine patients were retrospectively enrolled. PTD was defined as symptomatic thyroid disorder requiring long-term specific treatment. On the first PET performed during follow-up, maximal standardized uptake value of the thyroid (SUVmax-Th) and SUVmax-Th/SUVmax-blood-pool ratio (Th/B) were measured. Areas under ROC curves (AUC) of these parameters for the diagnostic of PTD were compared. Cutoff values were defined to maximize the Youden's index. Survival analyses were performed according to the Kaplan-Meier method and compared using the log-rank method between patients with and without enhanced thyroid uptake according to cutoff values defined with the Hothorn and Lausen method. RESULTS: Four patients presented PTD. Median SUVmax-Th and Th/B were, respectively, 2.11 and 1.00. The median follow-up period was 21.7 months. AUC were 1.0 (CI95% 0.88-1.0) for both parameters. Optimal cutoff values were, respectively, SUVmax-Th > 4.1 and Th/B > 2.0, both conferring sensitivities of 100% (CI95% 40-100%) and specificities of 100% (CI95% 86-100%). The median progression-free survival and overall survival were 11.3 months and 33.5 months, respectively. Using optimized cutoffs, there was no statistically significant difference of survival. CONCLUSION: SUVmax-Th > 4.1 and Th/B > 2.0 provided perfect diagnostic performances to detect patients that developed PTD. No significant survival difference was found between patients with and without increased thyroid uptake.