Phase II Trial Assessing the Repeatability and Tumor Uptake of [68Ga]Ga-HER2 Single-Domain Antibody PET/CT in Patients with Breast Carcinoma.

Human epidermal growth factor receptor 2 (HER2) status is used for decision-making in breast carcinoma treatment. The status is obtained through immunohistochemistry or in situ hybridization. These two methods have the disadvantage of necessitating tissue sampling, which is prone to error due to tumor heterogeneity or interobserver variability. Whole-body imaging might be a solution to map HER2 expression throughout the body. Methods: Twenty patients with locally advanced or metastatic breast carcinoma (5 HER2-positive and 15 HER2-negative patients) were included in this phase II trial to assess the repeatability of uptake quantification and the extended safety of the [68Ga]Ga-NOTA-anti-HER2 single-domain antibody (sdAb). The tracer was injected, followed by a PET/CT scan at 90 min. Within 8 d, the procedure was repeated. Blood samples were taken for antidrug antibody (ADA) assessment and liquid biopsies. On available tissues, immunohistochemistry, in situ hybridization, and mass spectrometry were performed to determine the correlation of HER2 status with uptake values measured on PET. If relevant preexisting [18F]FDG PET/CT images were available (performed as standard of care), a comparison was made. Results: With a repeatability coefficient of 21.8%, this imaging technique was repeatable. No clear correlation between PET/CT uptake values and pathology could be established, as even patients with low levels of HER2 expression showed moderate to high uptake. Comparison with [18F]FDG PET/CT in 16 patients demonstrated that in 7 patients, [68Ga]Ga-NOTA-anti-HER2 shows interlesional heterogeneity within the same patient, and [18F]FDG uptake did not show the same heterogeneous uptake in all patients. In some patients, the extent of disease was clearer with the [68Ga]Ga-NOTA-anti-HER2-sdAb. Sixteen adverse events were reported but all without a clear relationship to the tracer. Three patients with preexisting ADAs did not show adverse reactions. No new ADAs developed. Conclusion: [68Ga]Ga-NOTA-anti-HER2-sdAb PET/CT imaging shows similar repeatability to [18F]FDG. It is safe for clinical use. There is tracer uptake in cancer lesions, even in patients previously determined to be HER2-low or -negative. The tracer shows potential in the assessment of interlesional heterogeneity of HER2 expression. In a subset of patients, [68Ga]Ga-NOTA-anti-HER2-sdAb uptake was seen in lesions with no or low [18F]FDG uptake. These findings support further clinical development of [68Ga]Ga-NOTA-anti-HER2-sdAb as a PET/CT tracer in breast cancer patients.

18F-FDG PET/CT in Waldenström associated amyloidosis.

Amyloidoisis in patients with Waldenström macroglobulinemia (WM) mostly involves the heart, peripheral nerves and kidneys. Retroperitoneal amyloidosis is a rare finding. We describe a 62-year-old man with an incidental finding of a monoclonal gammopathy and elevated inflammatory parameters. Bilateral moderately active retroperitoneal infiltration with punctiform calcifications was found on fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging. Taken together, these findings are suggestive of Waldenström associated amyloidosis. Computed tomography-guided retroperitoneal biopsy confirmed the diagnosis.

Direct prospective comparison of 18F-FDG PET and arterial spin labelling MR using simultaneous PET/MR in patients referred for diagnosis of dementia.

PURPOSE: 18F-FDG PET is routinely used as an imaging marker in the early and differential diagnosis of dementing disorders and has incremental value over the clinical neurological and neuropsychological evaluation. Perfusion MR imaging by means of arterial spin labelling (ASL) is an alternative modality to indirectly measure neuronal functioning and could be used as complement measurement in a single MR session in the workup of dementia. Using simultaneous PET-MR, we performed a direct head-to-head comparison between enhanced multiplane tagging ASL (eASL) and 18F-FDG PET in a true clinical context of subjects referred for suspicion of neurodegenerative dementia. METHODS: Twenty-seven patients underwent a 20-min 18F-FDG PET/MR and simultaneously acquired eASL on a GE Signa PET/MR. Data were compared with 30 screened age- and gender-matched healthy controls. Both integral eASL and 18F-FDG datasets were analysed visually by two readers unaware of the final clinical diagnosis, either in normal/abnormal classes, or full differential diagnosis (normal, Alzheimer type dementia [AD], dementia with Lewy Bodies [LBD], frontotemporal dementia [FTD] or other). Reader confidence was assessed with a rating scale (range 1-4). Data were also analysed semiquantitatively by VOI and voxel-based analyses. RESULTS: The ground truth diagnosis for the patient group resulted in 14 patients with a neurodegenerative cognitive disorder (AD, FTD, LBD) and 13 patients with no arguments for an underlying neurodegenerative cause. Visual analysis resulted in equal specificity (0.70) for differentiating normal and abnormal cases between the two modalities, but in a higher sensitivity (0.93), confidence rating (0.64) and interobserver agreement for 18F-FDG PET compared with eASL. The same was true for assigning a specific differential diagnosis (sensitivity: and 0.39 for 18F-FDG PET and eASL, respectively). Semiquantitative analyses revealed prototypical patterns for AD and FTD, with both higher volumes of abnormality and intensity differences on 18F-FDG PET. CONCLUSION: In a direct head-to-head comparison on a simultaneous GE Signa PET/MR, 18F-FDG PET performed better compared with ASL in terms of sensitivity and reader confidence, as well as volume and intensity of abnormalities. However, using pure semiquantitative analysis, similar diagnostic accuracy between the two modalities was obtained. Therefore, ASL may still serve as complement to neuroreceptor or protein deposition PET studies when a single simultaneous investigation is warranted.

Mesenteric Panniculitis With Lupus Demonstrated on 18F-FDG PET/CT.

We describe the F-FDG PET/CT findings in a rare case of mesenteric panniculitis caused by systemic lupus. A previous CT had raised suspicion of a space-occupying lesion in the left hypochondrium in a context of aspecific constitutional symptoms and inflammatory parameters. The diagnosis of panniculitis was confirmed at laparoscopic biopsy directed by the PET findings. Follow-up F-FDG PET/CT after 1 month of corticosteroid therapy showed complete disappearance of the abdominal hypermetabolic foci.

Bone Scintigraphy in Poststreptococcal Periostitis With Dysproteinemia.

A 39-year-old man presented with severe bone pain in the tibiae and forearms in the wake of a poststreptococcal sepsis complicated with pneumonia and erysipelas 4 months earlier. Bone scintigraphy was indicative of periostitis of the tibia, ulna, and radius bilaterally, and in combination with the increased inflammatory parameters and dysproteinemia, the diagnosis of Goldbloom syndrome was made. Goldbloom syndrome is an idiopathic periosteal hyperostosis associated with dysproteinemia and elevated inflammatory parameters. Although it has only been described in children/adolescents, this case illustrates that, in the specific clinical and biochemical setting, it should also be considered in adults.

Negative 18F-FDG PET and positive CT and MRI findings in multifocal splenic hamartoma.

We report our fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18FFDG PET/CT) findings in a 51 years old female presenting with B symptoms, respectively fever, night sweats and malaise, that underwent an 18F-FDG PET/CT examination to exclude underlying lymphomatous disease. Whereas 18F-FDG PET scan findings were negative, CT put to evidence the presence of multiple small lesions suggestive for multifocal hamartoma. On a subsequently performed magnetic resonance imaging (MRI) of the spleen, multiple infracentimetric foci were visualized displaying characteristic findings for hamartoma. During a follow-up period of two years no change in size or characteristics of these lesions occurred. CONCLUSION: The normal :F-FDG PET/CT findings suggested that, at least in this patient, splenic hamartoma may display a similar :F-FDG avidity when compared to normal splenic tissue. Alternatively, due to the infra-centrimeric size of the hamartoma and spill-over from :F-FDG activity from neighbouring normal tissue, the true 18F-FDG avidity of the hamartomas present might also be overestimated.

Unilaterally Decreased Striatal Dopamine Transporter Caused by Venous Anomaly.

We describe a finding of unilaterally decreased binding of I-ioflupane in the basal ganglia in a 78-year-old woman that could be attributed to an underlying developmental venous anomaly.

Aspecific Uptake of 68GA-PSMA in Paget Disease of the Bone.

Ga-PSMA plays an increasing role in prostate cancer management, but several instances of false positivity have now been recognized. We present a patient with metastatic prostatic carcinoma who also showed overexpression of PSMA in Paget disease of the humerus on Ga-PSMA PET. This probably relates to bone remodeling and increased vascularity. It is important to be aware of this aspecific uptake because its recognition may avoid overstaging and may alter the therapeutic choice.

Incidental finding of silent appendicitis on (18)F-FDG PET/CT in a patient with small cell lung adenocarcinoma.

We report the incidental diagnosis of acute asymptomatic appendicitis on a fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography ((18)F-FDG PET/CT) performed for staging of a non small cell lung carcinoma. The patient was asymptomatic and laboratory tests were normal. The case illustrates: a) the possibility to diagnose appendicitis on (18)F-FDG PET/CT and b) the possibility of silent acute appendicitis, although this is a rare occurrence.

PET imaging shows loss of striatal PDE10A in patients with Huntington disease.

Phosphodiesterase 10A (PDE10A) belongs to a family of enzymes that hydrolyze cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate.(1) PDE10A is highly enriched in striatal medium spiny neurons (MSNs), where it regulates intracellular signaling.(1) PDE10A has been proposed as a therapeutic target for Huntington disease (HD), a disorder that preferentially affects MSNs, based on the observation that pharmacologic inhibition of PDE10A in transgenic HD mice significantly improved behavioral and neuropathologic abnormalities.(2) However, earlier work had shown that striatal PDE10A levels in HD mice already decline to minimal levels before onset of motor symptoms,(3) possibly because mutant huntingtin represses PDE10A transcription. Also, postmortem analysis of striatum of 3 patients with HD revealed strong reduction of PDE10A levels.(3) Depletion of PDE10A in HD striatum would at first sight seem hard to reconcile with a beneficial effect of PDE10A inhibitors in HD. However, a recent study reported a dramatic increase, rather than decrease, of PDE10A protein in MSNs of HD mice.(4) In light of these conflicting results and the strong interest in development of PDE10A inhibitors for clinical use in HD, it is important to determine whether PDE10A levels are affected in the striatum of patients with HD in vivo.