Gastrin Releasing Peptide Receptors-targeted PET Diagnostics and Radionuclide Therapy for Prostate Cancer Management:Preclinical and Clinical Developments of the Past 5 Years

Prostate cancer (PC) remains one of the most prevalent cancer types accounting for 7.3% of all cancer cases in 2020.1 The 5 year survival rate of patients with local or regional disease is greater than 99%, but despite major developments made, the 5 year survival rate of advanced disease remains a mere 35%.2 Accordingly, research is focused on developing novel interventions for early detection and more effective treatment

Recruitment into antibody prevalence studies: a randomized trial of postcards vs. letters as invitations

Abstract Background In a potential epidemic of an emerging infection, representative population-based serologic studies are required to determine the extent of immunity to the infectious agent, either from natural infection or vaccination. Recruitment strategies need to optimize response rates. Methods Within a seroepidemiologic study to determine the true burden of SARS-CoV2 infection in two Bay Area counties, we evaluated whether letter (L) or postcard (P) invitations with reminders were more effective at recruiting participant households. Using geographic, probability-based sampling, 9,999 representative addresses, split between Santa Clara and Solano counties, were randomized to receive an initial invitation (L or P); a randomized reminder mailing sent two weeks later to all non-respondents created four mailing type groups (L/L, L/P, P/L, P/P). Interested households provided contact information via survey to perform blood spot collection at home for testing and then receive SARS-CoV2 serology results. Comparison of demographics among respondents and non-respondents used census tract data. Results Receiving any reminder mailing increased household response rates from 4.2% to between 8–13% depending on mailing combination. Response rates from two letters were 71% higher than from two postcards (13.2% vs. 7.7%, OR = 1.83 [95% CI: 1.5–2.2]). Respondents were older, more educated and more likely white than non-respondents. Compared to Solano county, Santa Clara county had different demographics and increased household response rates (L/L: 15.7% vs 10.7%; P/P: 9.2% vs. 6.1%; p < 0.0001); the effect of mailing types, however, was the same (L/L vs. P/P: Santa Clara: OR = 1.83 [95% CI: 1.4–2.3]; Solano: OR = 1.84 [95% CI:1.4–2.5]). Conclusion Letters, as both invitations and reminders, are a more effective recruitment tool than postcards and should be considered when seeking a representative population-based sample for serological testing

The role of SPECT/CT in radioembolization of liver tumours

Radioembolization (RE) with 90Y microspheres is a promising catheter-based therapeutic option for patients with unresectable primary and metastatic liver tumours. Its rationale arises from the dual blood supply of liver tissue through the hepatic artery and the portal vein. Metastatic hepatic tumours measuring >3 mm derive 80-100 % of their blood supply from the arterial rather than the portal hepatic circulation. Typically, an angiographic evaluation combined with 99mTc-macroaggregated albumin (99mTc-MAA) scan precedes therapy to map the tumour feeding vessels as well as to avoid the inadvertent deposition of microspheres in organs other than the liver. Prior to administration of 99mTc-M AA, p ro p hylactic coil embolization of the gastroduodenal artery is recommended to avoid extrahepatic deposition of the microspheres. SPECT/CT allows direct correlation of anatomic and functional information in patients with unresectable liver disease. SPECT/CTis recommended to assess intrahepatic distribution as well as extrahepatic gastrointestinal uptake in these patients. Pretherapeutic SPECT/CT is an important component of treatment planning including catheter positioning and dose finding. A post-therapy bremsstrahlung (BS) scan should follow RE to verify the distribution of the administered tracer. BS SPECT/CT imaging enables better localization and definition of intrahepatic and possible extrahepatic sphere distribution and to a certain degree allows posttreatment dosimetry. In this paper we address the usefulness and significance of SPECT/CT in therapy planning and therapy monitoring of RE. © Springer-Verlag Berlin Heidelberg 2014

A Visual Pathway into Central Complex for High-Frequency Motion-Defined Bars in Drosophila

Relative motion breaks a camouflaged target from a same-textured background, thus eliciting discrimination of a motion defined object. Ring (R) neurons are critical components in the Drosophila central complex, which has been implicated in multiple visually guided behaviors. Using two-photon calcium imaging with female flies, we demonstrated that a specific population of R neurons that innervate the superior domain of bulb neuropil, termed superior R neurons, encoded a motion defined bar with high spatial frequency contents. Upstream superior tuberculo-bulbar (TuBu) neurons transmitted visual signals by releasing acetylcholine within synapses connected with superior R neurons. Blocking TuBu or R neurons impaired tracking performance of the bar, which reveals their importance in motion-defined feature encoding. Additionally, the presentation of a low spatial frequency luminance-defined bar evoked consistent excitation in R neurons of the superior bulb, whereas either excited or inhibited responses were evoked in the inferior bulb. The distinct properties of the responses to the two bar stimuli indicate there is a functional division between the bulb subdomains. Moreover, physiological and behavioral tests with restricted lines suggest that R4d neurons play a vital role in tracking motion-defined bars. We conclude that the central complex receives the motion-defined features via a visual pathway from superior TuBu to R neurons and might encode different visual features via distinct response patterns at the population level, thereby driving visually guided behaviors

Biodistribution of a Mitochondrial Metabolic Tracer, [18F]F-AraG, in Healthy Volunteers

Purpose[18F]F-AraG is a radiolabeled nucleoside analog that shows relative specificity for activated T cells. The aim of this study was to investigate the biodistribution of [18F]F-AraG in healthy volunteers and assess the preliminary safety and radiation dosimetry.MethodsSix healthy subjects (three female and three male) between the ages of 24 and 60 participated in the study. Each subject received a bolus venous injection of [18F]F-AraG (dose range: 244.2-329.3 MBq) prior to four consecutive PET/MR whole-body scans. Blood samples were collected at regular intervals and vital signs monitored before and after tracer administration. Regions of interest were delineated for multiple organs, and the area under the time-activity curves was calculated for each organ and used to derive time-integrated activity coefficient (TIAC). TIACs were input for absorbed dose and effective dose calculations using OLINDA.ResultsPET/MR examination was well tolerated, and no adverse effects to the administration of [18F]F-AraG were noted by the study participants. The biodistribution was generally reflective of the expression and activity profiles of the enzymes involved in [18F]F-AraG's cellular accumulation, mitochondrial kinase dGK, and SAMHD1. The highest uptake was observed in the kidneys and liver, while the brain, lung, bone marrow, and muscle showed low tracer uptake. The estimated effective dose for [18F]F-AraG was 0.0162 mSv/MBq (0.0167 mSv/MBq for females and 0.0157 mSv/MBq for males).ConclusionBiodistribution of [18F]F-AraG in healthy volunteers was consistent with its association with mitochondrial metabolism. PET/MR [18F]F-AraG imaging was well tolerated, with a radiation dosimetry profile similar to other commonly used [18F]-labeled tracers. [18F]F-AraG's connection with mitochondrial biogenesis and favorable biodistribution characteristics make it an attractive tracer with a variety of potential applications