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Abstract Background Neuropsychiatric sequelae of COVID-19 have been widely documented in patients with severe neurological symptoms during the chronic or subacute phase of the disease. However, it remains unclear whether subclinical changes in brain metabolism can occur early in the acute phase of the disease. The aim of this study was to identify and quantify changes in brain metabolism in patients hospitalized for acute respiratory syndrome due to COVID-19 with no or mild neurological symptoms. Results Twenty-three non-intubated patients (13 women; mean age 55.5 ± 12.1 years) hospitalized with positive nasopharyngeal swab test (RT-PCR) for COVID-19, requiring supplemental oxygen and no or mild neurological symptoms were studied. Serum C-reactive protein measured at admission ranged from 6.43 to 189.0 mg/L (mean: 96.9 ± 54.2 mg/L). The mean supplemental oxygen demand was 2.9 ± 1.4 L/min. [18F]FDG PET/CT images were acquired with a median of 12 (4–20) days of symptoms. After visual interpretation of the images, semiquantitative analysis of [18F]FDG uptake in multiple brain regions was evaluated using dedicated software and the standard deviation (SD) of brain uptake in each region was automatically calculated in comparison with reference values of a normal database. Evolutionarily ancient structures showed positive SD mean values of [18F]FDG uptake. Lenticular nuclei were bilaterally hypermetabolic (> 2 SD) in 21/23 (91.3%) patients, and thalamus in 16/23 (69.6%), bilaterally in 11/23 (47.8%). About half of patients showed hypermetabolism in brainstems, 40% in hippocampi, and 30% in cerebellums. In contrast, neocortical regions (frontal, parietal, temporal and occipital lobes) presented negative SD mean values of [18F]FDG uptake and hypometabolism (

Introduction/Justification: We have recently demonstrated a 18F-FDG PET/CT image pattern of brain metabolic redistribution from the neocortex to evolutionary ancient brain structures during the acute phase of COVID-19 respiratory syndrome (1). We report here a patient with extensive lesions caused by Hodgkin's lymphoma whose PET/CT demonstrated changes in the cerebral distribution of FDG, with reduced uptake in the neocortex and a relative increase in the basal ganglia, similar to that observed in acute COVID-19 (1). Report: A 57-year-old female patient with a history of hypertension and hypothyroidism, presented with weight loss and generalized lymphadenopathy. Biopsy revealed nodular sclerosis classical Hodgkin's lymphoma subtype. 18F-FDG PET/CT was requested for staging. The images showed marked hypermetabolism in lymphadenopathy below and above the diaphragm, spleen, and bone marrow, consistent with lymphoma infiltration. Reduced radiotracer uptake was also observed in the cerebral neocortex and relatively increased uptake in the basal ganglia. Semiquantitative analysis of FDG uptake in multiple brain regions was conducted using dedicated software, and the standard deviation (SD) of brain uptake in each region was calculated compared to a normal database, using the whole brain as the reference region for normalization. Quantification revealed marked increased relative uptake in lenticular nuclei (13.7 SD), thalamus (4.6) and brainstem (3.7), and reduced uptake in the frontal, parietal, and temporal lobes (-3,9 to -0,1 SD). Before starting chemotherapy, the patient experienced weakness, multiple episodes of diarrhea, and decreased level of consciousness. She developed hemophagocytic syndrome, septic shock, and died 19 days after PET/CT. Aggressive lymphomas exhibit intense FDG uptake, often with a high tumor burden. This can elevate blood lactate levels, which would become an alternative energy substrate for the brain and, by competition, reduce FDG uptake, as suggested by Yi HK et al (2). This is also described in individuals engaged in intense exercise, where decreased FDG uptake may be attributed to potential lactate utilization by the brain (3). The relatively preserved FDG uptake in the basal ganglia could be viewed as a physiological protective mechanism in response to reduced glucose availability for the brain. The oldest parts of the brain are vital for survival and must be preserved to maintain essential life functions. Despite being an organ with one of the highest glucose demands, the brain lacks the ability to store metabolic products for later use. Therefore, during competition with neoplastic cells for the available energy substrate, metabolic redistribution could contribute to preserving essential brain functions. Conclusion: Patients with high tumor burden due to Hodgkin's lymphoma may exhibit not only a global reduction in cerebral glucose uptake but also a redistribution of glucose consumption from the neocortex to older brain structures which are essential for survival.

Introduction/Justification: Myelofibrosis, a clonal disorder of hematopoietic stem cells, is characterized by chronic bone marrow inflammation and progressive fibrosis, resulting in hypocellularity and the displacement of neoplastic cells to extramedullary organs such as the spleen and liver, leading to splenomegaly and hepatomegaly. Hematopoietic stem cell transplantation is currently the only curative treatment, with five-year survival rates ranging between 51% and 61%, underscoring the need for novel diagnostic and therapeutic strategies. In recent years, positron emission tomography combined with computed tomography (PET/CT) using 18F-fluorodeoxyglucose (18F-FDG) has emerged as a valuable tool for assessing the glycolytic activity of various neoplasms, although there are limited reports on its utility in myelofibrosis. Concurrently, interest has grown in using the prostate-specific membrane antigen (PSMA) tracer to evaluate the neoangiogenic activity of diverse neoplasms. This study aims to compare glycolytic activity and neoangiogenic activity, assessed through 18F-FDG and 18F-PSMA PET/CT imaging, respectively, in patients with myelofibrosis. Report: Three patients diagnosed with myelofibrosis, aged 69, 71, and 74 years, underwent PET/CT scans on consecutive days, acquired 60 minutes after intravenous administration of 0.1 mCi/kg of 18F-FDG and 90 minutes after intravenous injection of 0.1 mCi/kg of 18F-PSMA. The images were analyzed by two nuclear medicine physicians and a radiologist. The maximum standardized uptake value (SUV) of the bone marrow, as well as the SUV and dimensions of the liver and spleen, were measured. Two patients exhibited mild to moderate diffuse increased uptake of both 18F-FDG and 18F-PSMA in the bone marrow (SUV-FDG: 6.4 and 3.5; SUV-PSMA: 3.5 and 1.7). One of them displayed mild hepatomegaly (18.7 cm), and both had marked splenomegaly (21.5 and 30.3 cm). Liver and spleen uptake of 18F-FDG was close to normal in both patients (SUV-FDG: 2.4 to 3.1), while moderate uptake of 18F-PSMA was observed in these organs (SUV-PSMA: 5.6 to 8.4), at least partially physiological and expected for this radiopharmaceutical. The third patient, who had undergone splenectomy, did not exhibit significant uptake of either tracer in the bone marrow but displayed marked uptake of 18F-PSMA in the liver (SUV-PSMA = 14.8), possibly physiological, with normal 18F-FDG uptake (SUV-FDG = 3.9). Conclusion: Patients with myelofibrosis appear to exhibit variable degrees of glycolytic activity and neoangiogenesis in the bone marrow, as detected by PET/CT imaging with 18F-FDG and 18F-PSMA. The moderate to marked uptake of 18F-PSMA in the liver and spleen, at least partly physiological, along with the uptake in the bone marrow in some cases, may suggest a theranostic potential of this radiopharmaceutical in myelofibrosis.

Introduction/Justification: Triple-refractory multiple myeloma (MM) has a poor prognosis. It is a neoplasm with marked genomic heterogeneity, and recently, our group demonstrated marked uptake of 68Ga-PSMA-11 in some patients, suggesting the potential theranostic use of PSMA in selected cases (1). Herein, we report the initial treatment with 177Lu-PSMA in a patient with refractory MM. Report: A 76-year-old male patient with IgA/Kappa MM refractory to 6 therapeutic lines, including daratumumab, lenalidomide, and bortezomib, underwent PET/CT with 18F-PSMA-1007, showing marked tracer uptake in multiple osteolytic lesions, several with extensive soft tissue components. A PET/CT with 18F-FDG was also performed, revealing similar findings. A first dose of 7,400 MBq (200 mCi) of 177Lu-PSMA-I&T was administered. The procedure was well tolerated, with slight clinical improvement observed in the week following the infusion. Visual analysis of whole-body scans performed at 21h, 30h, and 7 days demonstrated moderate tracer uptake, lower than that observed with 18F-PSMA-1007. There was slight washout between images at 21h and 30h and moderate/significant washout after 7 days. After 4 weeks, PET/CTs with 18F-PSMA and 18F-FDG were repeated, showing similar findings to the initial scans, with a slight reduction in tracer uptake in some lesions. There was also an increase in the volume of some soft tissue lesions, attributed to post-treatment inflammation. The patient received a second dose of 7,400 MBq (200 mCi) of 177Lu-PSMA-I&T after 6 weeks, and whole-body scans were performed at 2h and 24h, also showing visually lower uptake compared to 18F-PSMA-1007. The patient experienced an intercurrent femoral fracture, limiting mobility for clinical evaluation and subsequent procedures, ultimately leading to their passing after a few days. Conclusion: This preliminary report suggests that treatment of MM with 177Lu-PSMA is feasible and well tolerated after 2 initial doses. The uptake of 177Lu-PSMA-I&T was visually lower than that of 18F-PSMA-1007, which does not seem to be solely explained by the different resolution of images obtained from different tracers and equipment. There was a slight clinical and imaging response after the first dose, out of a total of 6 planned. A fracture complication and the severity of the case prevented imaging evaluation after the 2nd dose and further treatment continuation. PSMA-177Lu therapy in MM treatment appears to be safe with an initial favorable response, albeit slight. Studies with complete treatments (6 cycles) and in clinically less severe patients are needed to assess the effectiveness of the procedure.