Diagnostic performance of 18F-DCFPyL positron emission tomography/computed tomography for biochemically recurrent prostate cancer and change-of-management analysis.

INTRODUCTION: Conventional imaging (CI) performs poorly to identify sites of disease in biochemically recurrent prostate cancer. 68Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) is most studied but has a very short half-life. This study reports the diagnostic performance of the novel prostate-specific membrane antigen (PSMA) radiotracer 18F-DCFPyL using real-life data and tumor board simulation to estimate the impact of 18F-DCFPyL PET on patient management. METHODS: Ninety-three 18F-DCFPyL PET/CT scans performed for patients previously treated for prostate cancer with a rising prostate-specific antigen (PSA) were retrospectively compared to contemporary CI and clinical imaging and PSA followups. A chart review was performed to document prior imaging, pathology results, serial serum PSA measurements, and other pertinent clinical data. Clinical utility of 18F-DCFPyL PET was measured using a simulated tumor board formed by three physicians with extensive prostate cancer experience deciding on management with and without knowledge of PET/CT results. RESULTS: At median PSA 2.27 (interquartile rage [IQR] 5.27], 82% of 18F-DCFPyL PET/CT demonstrated at least one site of disease: non-regional lymph nodes (37% of scans), regional lymph node metastases (28%), local recurrence (27%), and bone metastases (20%), with higher PET positivity at higher PSA. Compared to 18F-DCFPyL PET/CT, CI showed overall poor performance, with accuracy below 20% for all extent of disease. PET/CT changed management in 44% of cases. The most frequent scenario was a radical change from initiating androgen deprivation therapy (ADT) to stereotactic body radiotherapy (SBRT) of oligo-lesional disease. In univariate and multivariate analysis, no patient characteristic could predict change of management by PET/CT results. CONCLUSIONS: 18F-DCFPyL significantly outperforms CI in recurring prostate cancer and is likely to impact management.

Exposure of Avian Embryos to Cycling Incubation Temperatures Reduces Adult Bactericidal Ability.

In birds, the temperature at which eggs are incubated shapes many aspects of hatchling phenotype, but long-term effects are less studied. We studied the effect of incubation temperature and pattern on the subsequent development of innate immune function in Japanese quail (Coturnix japonica). We incubated quail eggs in one of three replicated treatments: control (37.5°C), low (36.0°C), and cyclical incubation. The cyclical treatment had the same average temperature as the low-temperature treatment (36.0°C) and an upper temperature that was the same as the control. When individuals were 5, 20, and 55 d of age (i.e., adults), we measured the ability of blood plasma to kill Escherichia coli. Throughout development there was a nonsignificant trend for immune function to be lower in the cycling treatment. In adulthood, however, individuals incubated at cycling temperatures had significantly lower immune function than control birds but did not differ from individuals incubated at constant low temperatures. Males and females responded similarly to the incubation treatment, but females developed a greater plasma bactericidal ability than males. We conclude that variation in innate immune function of adult birds is shaped by temperature fluctuations experienced during incubation.

Maternal immunization increases nestling energy expenditure, immune function, and fledging success in a passerine bird.

Female birds transfer maternally derived antibodies (matAb) to their nestlings, via the egg yolk. These antibodies are thought to provide passive protection, and allow nestlings to avoid the costs associated with mounting an innate immune response. To test whether there is an energetic benefit to nestlings from receiving matAb, we challenged adult female tree swallows (Tachycineta bicolor) prior to clutch initiation with either lipopolysaccharide (LPS) or saline (Control). Following hatching, one half of each female's nestlings were immunized on day 8 post-hatch with LPS or saline, and the 4-h post-immunization nestling metabolic rate (MR) was measured. There was no difference in either LPS-reactive antibodies or total Ig levels between offspring of immunized and non-immunized mothers on day 6 or 14 post-hatch, possibly reflecting a relatively short half-life of matAbs in altricial birds. Additionally, we found no evidence that nestlings from LPS-immunized mothers could avoid the growth suppression that may result from activation of an inflammatory response. Unexpectedly, we found that control nestlings from LPS mothers had higher resting MR than control nestlings of control mothers. We attribute the increased MR to the costs associated with a general non-specific enhancement of immune function in nestlings from LPS-immunized mothers. Consistent with enhanced immune function, nestlings of immunized mothers had a more robust inflammatory response to phytohaemagglutinin and higher fledging success. Our results suggest that maternal antigen exposure pre-laying can result in increased fitness for both mothers and offspring, depending on food availability.

Constant and Cycling Incubation Temperatures Have Long-Term Effects on the Morphology and Metabolic Rate of Japanese Quail.

Incubation temperature can have profound effects on growth and development of embryos and young birds. However, few studies have examined the role that cycling incubation temperature may play in phenotypic variation and whether these effects persist to adulthood. We incubated Japanese quail eggs at control temperatures (37.5°C), at low temperatures (36.0°C), and under a cyclical treatment that maintained the same average temperature as the low treatment (36.0°C) with high temperatures that were the same as the control (37.5°C) and low temperatures that still allowed for development of the embryo (28.0°C). Individuals in the low treatment group were smaller in mass and size than individuals in the control group but had an increased basal metabolic rate relative to individuals in the cyclical treatment group. Temperature cycling offset the effects of low incubation temperatures on metabolic rate and embryonic development but not the effects on adult mass and size. Although Japanese quail are sexually size dimorphic, with females larger than males, we could detect no evidence of sex-specific sensitivity to suboptimal incubation temperatures. These results highlight the importance of incubation temperature and pattern as sources of morphological and physiological variation of adult birds.