Prognostic role of pretreatment 18F-FDG PET/CT in primary brain lymphoma.

OBJECTIVE: Primary brain lymphoma is an aggressive extranodal non-Hodgkin lymphoma with poor prognosis. Many possible prognostic factors are investigated with controversial results, but possible prognostic role of 18fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) features remains unclear. Our aim was to study the metabolic behavior of brain lymphoma at 18F-FDG PET/CT and the prognostic impact of qualitative and semiquantitative PET/CT parameters. METHODS: Between 2006 and 2018, 52 patients (26 females and 26 males; mean age: 61 years) with histologically confirmed diagnosis of brain lymphoma who underwent 18F-FDG PET/CT for staging before any treatment were included. PET images were qualitatively and semiquantitatively analyzed by measuring the maximum standardized uptake value body weight (SUVbw), lean body mass (SUVlbm), body surface area (SUVbsa), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The Kaplan-Meier method was used to estimate the progression-free survival (PFS) and overall survival (OS) times. Cox regression models were performed to determinate the relation between qualitative and semiquantitative PET/CT features and OS and PFS. RESULTS: Thirty-nine patients had positive 18F-FDG PET/CT showing 18F-FDG uptake (mean SUVbw of 18.2; SUVlbm of 13.9; SUVbsa of 5; MTV of 14.8; TLG of 153) at the corresponding cerebral lesion; the remaining 13 were not 18F-FDG avid. Relapse or progression of disease occurred in 22 patients with an average time of 9.7 months; death occurred in 18 patients with an average of 7.9 months. There was no difference in PFS and OS between baseline PET/CT positive and negative groups or considering SUVbw, SUVlbm, and SUVbsa. PFS and OS was significantly shorter in patients with MTV ≥ 9.8 cm3 (p = 0.037 and p = 0.022, respectively) and TLG ≥ 94 (p = 0.045 and p = 0.0430, respectively). CONCLUSIONS: 18F-FDG avidity was noted in 75% of cases. Only metabolic tumor parameters (MTV and TLG) were independently correlated with PFS and OS.

Comparison between the summed difference score and myocardial blood flow measured by 13N-ammonia.

BACKGROUND: Both the myocardial perfusion pattern and myocardial blood flow (MBF) are used to assess patients with suspected coronary artery disease (CAD). The aim of this study was to compare the perfusion pattern (using the summed difference score [SDS]) to MBF in a consecutive group of patients undergoing PET/CT with 13 N-ammonia (13NH3). METHODS: 47 consecutive patients, aged 65 ± 12 years (42 men) with known or suspected CAD, underwent vasodilator stress/rest PET/CT with 13NH3 for clinical indications. The SDS was determined by a commercially available software based on a 17-segment model. MBF was measured at rest and during hyperemia by dynamic acquisition and single-compartment model analysis. From the rest and stress MBF, the absolute difference (stress-rest) in myocardial blood flow defined as difference in myocardial blood flow (DMBF) was derived. RESULTS: There were no significant differences between patients with no ischemia (SDS ≤ 1) and those with ischemia (SDS > 1) in CFR (2.84 ± 0.73 vs 2.63 ± 0.89, P = NS) and DMBF (1.34 ± 0.45 vs 1.24 ± 0.53 mL·minute-1·g-1, P = NS). There were however significant regional differences (141 different vascular territories in 47 patients) between these two groups (CFR: 2.84 ± 0.95 vs 2.16 ± 0.57, P < .001 and DMBF: 1.39 ± 0.6 vs 0.87 ± 0.39, P < .0001). The correlation between regional CFR and regional DMBF with SDS was significant (y = 2.7145e-0.059x R = 0.358 and y = 1.2769e-0.119x R = 0.44) CONCLUSION: The SDS is the difference between two measurements (stress-rest) and it correlates better with regional DMBF, which is another measurement that reflects the difference between stress and rest. The correlation is better on regional than global basis.

The strange case of the [13N]NH3: validation of the production process for human use.

OBJECTIVE: PET radiopharmaceuticals are often injected in patients before all quality controls are performed and before sterility results are available. We propose a process validation to produce very safe and pure [N]NH3 for human use. METHODS: [N]NH3 was produced in the cyclotron target. Online purification was performed by anionic exchange resin. All the production steps were subjected to a sterility test. Some additional controls were added to those required by the monograph. RESULTS: The radiochemical yield of the syntheses was 26.3 and 61.5% corrected for decay, with a radiochemical purity of 100%. In addition to quality controls requested by the European Pharmacopeia monograph, we carefully analyzed the product for the presence of possible contaminants. Some elements, mainly metals, were found in very low amounts at concentrations in the range of ppb. The radionuclidic purity was verified. The achievement of the parameters of osmolality, by addition of saline solution to the preparation, made the analysis of chemical purity difficult and worsened the measurement of radiochemical purity by high performance liquid chromatography. Only pH control is necessary before administration to patients and therefore a safe production process was set up to prevent microbiological contamination. All phases were carefully standardized, starting from in-target production of [N]NH3, to final splitting in the syringes. Sterility tests showed no bacterial growth, indicating the safety of the production process. CONCLUSION: All our syntheses followed the monograph indications and were optimal to obtain PET imaging of a patient's myocardium.

Drop of connexins: a possible link between aging and cancer?

The incidence of cancer increases with age but we do not know why. As a working hypothesis we propose here that cells somehow initiated in vivo in the course of life and finally engaged in the aging program, which involves a drop of connexins with loss of cell-to-cell communication (equivalent to the promotion phase in the multistep process of carcinogenesis), may recover their growth potential, thus allowing cancer to progress. This is supported by evidence that: (i) connexin 43 (Cx43) acts as a tumor suppressor; (ii) cx43 and gap junction intercellular communication drop in precancerous lesions and in tumors of various origins, as well as in aging cells; (iii) telomerase is activated in cancerous somatic cells.

Drop of connexin 43 in replicative senescence of human fibroblasts HEL-299 as a possible biomarker of senescence.

The expression of connexin 43 (cx43) and cell-cell communication were studied in replicative senescence of cultured HEL-299 fibroblasts. A progressive decrease in fluorescent dye transfer was detected by a scrape-loading technique in aging fibroblasts. This change was accounted for by a marked decrease in the amount of cx43 in aging cells, as detected by western blot analysis (cell extracts) and indirect fluorescence (cells in culture). However, semiquantitative RT-PCR assays of cx43 mRNA did not reveal appreciable changes, which suggests several possible explanations for the mechanism(s) underlying the decrease of cx43 in aging cells. These findings support the idea that the reduced expression of cx43 might be a biomarker of cell senescence.