The Angels agreed to terms with right-hander reliever Daniel Hudson on a Minor League deal to add bullpen depth, a source confirmed to MLB.com on Friday.

The Angels announced their Minor League coaching staffs on Saturday, including former Major League catcher Lou Marson being named the new manager of Triple-A Salt Lake and former big leaguer David Newhan as the new skipper at Double-A Birmingham.

The Angels added a veteran lefty reliever, as Dan Jennings officially signed a Minor League deal on Saturday and joined the club for workouts at the club's Spring Training complex. Jennings will earn $1 million, plus incentives, if he makes the club.

Radiolabeled small-molecule DOTA-haptens can be combined with antitumor/anti-DOTA bispecific antibodies (BsAbs) for pretargeted radioimmunotherapy (PRIT). For optimized delivery of the theranostic - and β-emitting isotope ¹⁷⁷Lu with DOTA-based PRIT (DOTA-PRIT), bivalent Gemini (DOTA-Bn-thiourea-PEG4-thiourea-Bn-DOTA, aka (3,6,9,12-tetraoxatetradecane-1,14-diyl)bis(DOTA-benzyl thiourea)) was developed. Methods: Gemini was synthesized by linking 2 S-2-(4-isothiocyanatobenzyl)-DOTA molecules together via a 1,14-diamino-PEG4 linker. [¹⁷⁷Lu]Lu-Gemini was prepared with no-carrier-added ¹⁷⁷LuCl₃ to a molar-specific activity of 123 GBq/μmol and radiochemical purity of more than 99%. The specificity of BsAb-¹⁷⁷Lu-Gemini was verified in vitro. Subsequently, we evaluated biodistribution and whole-body clearance for [¹⁷⁷Lu]Lu-Gemini and, for comparison, our gold-standard monovalent [¹⁷⁷Lu]Lu-S-2-(4-aminobenzyl)-DOTA ([¹⁷⁷Lu]Lu-DOTA-Bn) in naïve (tumor-free) athymic nude mice. For our proof-of-concept system, a 3-step pretargeting approach was performed with an established DOTA-PRIT regimen (anti-GPA33/anti-DOTA IgG-scFv BsAb, a clearing agent, and [¹⁷⁷Lu]Lu-Gemini) in mouse models. Results: Initial in vivo studies showed that [¹⁷⁷Lu]Lu-Gemini behaved similarly to [¹⁷⁷Lu]Lu-DOTA-Bn, with almost identical blood and whole-body clearance kinetics, as well as biodistribution and mouse kidney dosimetry. Pretargeting [¹⁷⁷Lu]Lu-Gemini to GPA33-expressing SW1222 human colorectal xenografts was highly effective, leading to absorbed doses of [¹⁷⁷Lu]Lu-Gemini for blood, tumor, liver, spleen, and kidneys of 3.99, 455, 6.93, 5.36, and 14.0 cGy/MBq, respectively. Tumor–to–normal tissue absorbed-dose ratios (i.e., therapeutic indices [TIs]) for the blood and kidneys were 114 and 33, respectively. In addition, we demonstrate that the use of bivalent [¹⁷⁷Lu]Lu-Gemini in DOTA-PRIT leads to improved TIs and augmented [¹⁷⁷Lu]Lu-Gemini tumor uptake and retention in comparison to monovalent [¹⁷⁷Lu]Lu-DOTA-Bn. Finally, we established efficacy in SW1222 tumor-bearing mice, demonstrating that a single injection of anti-GPA33 DOTA-PRIT with 44 MBq (1.2 mCi) of [¹⁷⁷Lu]Lu-Gemini (estimated tumor-absorbed dose, 200 Gy) induced complete responses in 5 of 5 animals and a histologic cure in 2 of 5 (40%) animals. Moreover, a significant increase in survival compared with nontreated controls was noted (maximum tolerated dose not reached). Conclusion: We have developed a bivalent DOTA-radiohapten, [¹⁷⁷Lu]Lu-Gemini, that showed improved radiopharmacology for DOTA-PRIT application. The use of bivalent [¹⁷⁷Lu]Lu-Gemini in DOTA-PRIT, as opposed to monovalent [¹⁷⁷Lu]Lu-DOTA-Bn, allows curative treatments with considerably less administered ¹⁷⁷Lu activity while still achieving high TIs for both the blood (>100) and the kidneys (>30).

To date, the imaging and diagnosis of hepatocellular carcinoma (HCC) rely on CT/MRI, which have well-known limitations. Glypican-3 (GPC3) is a cell surface receptor highly expressed by HCC but not by normal or cirrhotic liver tissue. Here we report initial clinical results of GPC3-targeted PET imaging with [⁶⁸Ga]Ga-DOTA-RYZ-GPC3 (RAYZ-8009), a peptide-based GPC3 ligand in patients with known or suspected HCC. Methods: [⁶⁸Ga]Ga-RAYZ-8009 was obtained after labeling the peptide precursor with ⁶⁸Ga from a ⁶⁸Ge/⁶⁸Ga generator and heating at 90°C for 10 min followed by sterile filtration. After administration of [⁶⁸Ga]Ga-RAYZ-8009, a dynamic or static PET/CT scan was acquired between 45 min and 4 h after administration. Radiotracer uptake was measured by SUVs for the following tissues: suspected or actual HCC or hepatoblastoma lesions, non–tumor-bearing liver, renal cortex, blood pool in the left ventricle, and gastric fundus. Additionally, tumor–to–healthy-liver ratios (TLRs) were calculated. Results: Twenty-four patients (5 patients in the dynamic protocol; 19 patients in the static protocol) were scanned. No adverse events occurred. Two patients had no lesion detected and did not have HCC during follow-up. In total, 50 lesions were detected and analyzed. The mean SUV_max of these lesions was 19.6 (range, 2.7–95.3), and the mean SUV_mean was 10.1 (range, 1.0–49.2) at approximately 60 min after administration. Uptake in non–tumor-bearing liver and blood pool rapidly decreased over time and became negligible 45 min after administration (mean SUV_mean, <1.6), with a continuous decline to 4 h after administration (mean SUV_mean, 1.0). The opposite was observed for HCC lesions, for which SUVs and TLRs continuously increased for up to 4 h after administration. In individual lesion analysis, TLR was the highest between 60 and 120 min after administration. Uptake in the gastric fundus gradually increased for up to 45 min (to an SUV_max of 31.3) and decreased gradually afterward. Conclusion: [⁶⁸Ga]Ga-RAYZ-8009 is safe and allows for high-contrast imaging of GPC3-positive HCC, with rapid clearance from most normal organs. Thereby, [⁶⁸Ga]Ga-RAYZ-8009 is promising for HCC diagnosis and staging. Further research is warranted.

This study evaluates the diagnostic utility of PET/MRI for primary, locoregional, and nodal head and neck squamous cell carcinoma (HNSCC) through systematic review and metaanalysis. Methods: A systematic search was conducted using PubMed and Scopus to identify studies on the diagnostic accuracy of PET/MRI for HNSCC. The search included specific terms and excluded nonhybrid PET/MRI studies, and those with a sample size of fewer than 10 patients were excluded. Results: In total, 15 studies encompassing 638 patients were found addressing the diagnostic test accuracy for PET/MRI within the chosen subject domain. Squamous cell carcinoma of the nasopharynx was the most observed HNSCC subtype (n = 198). The metaanalysis included 12 studies, with pooled sensitivity and specificity values of 93% and 95% per patient for primary disease evaluation, 93% and 96% for locoregional evaluation, and 89% and 98% per lesion for nodal disease detection, respectively. An examination of a subset of studies comparing PET/MRI against PET/CT or MRI alone for evaluating nodal and locoregional HNSCC found that PET/MRI may offer slightly higher accuracy than other modalities. However, this difference was not statistically significant. Conclusion: PET/MRI has excellent potential for identifying primary, locoregional, and nodal HNSCC.

The Japanese parliament on Monday re-elected Liberal Democratic Party chief Shigeru Ishiba as prime minister in a rare runoff vote after the ruling LDP lost its majority in the lower legislative chamber.

An Illinois woman tucked a Lucky Day Lotto ticket into her purse and forgot about it before discovering it was a $1 million winner.

A coyote that had a plastic jug stuck over its head for at least a week was rescued by members of the public in Illinois and is now recovering at a wildlife rescue.

Zack Ostapchuk returns to Belleville after posting one assist in six games with the big club.

Nearly 17 million children lack high-speed internet at home that's considered crucial to their ability to participate in remote learning during the pandemic, according to a new study.

David Schuler, the superintendent of Township High School District 214 in Arlington Heights, Ill., has been named 2018 National Superintendent of the Year.

A union lobbyist who worked just one day as a substitute teacher is entitled to a pension worth potentially tens of thousands of dollars annually, the Illinois supreme court has ruled.

The state's budget bill, which Republican Gov. Bruce Rauner signed into law this week, caps annual raises for end-of-career-teachers, lowering the pension they can receive.

Lawmakers in Illinois are considering a bill that would require children to start kindergarten if they are 5 on or before May 31, with exceptions for summer birthdays.

This Quality Counts 2019 Highlights Report captures all the data you need to assess your state's performance on key educational outcomes.

The state's decision indicates that U.S. Secretary of Education Betsy DeVos' push on COVID-19 and private school students is having an affect.

This Quality Counts 2020 Highlights Report captures all the data you need to assess your state's performance on key educational outcomes.

The court declined to take up an appeal backed by school groups of a ruling allowing some property taxpayers challenge their assessments in federal court.

Danilo De Gregorio
Feb 3, 2021; 41:891-900
Symposium and Mini-Symposium

A new study from Smithsonian scientists analyzes ant and fungus species, and uncovers the origins of their close partnership

A paleontologist at the Natural History Museum in London chronicles the age of the famous and fascinating massive reptiles

Credit: David Marshall, University of Bristol

A night at the museum with the Smithsonian's "Laser Cowboys" http://j.mp/17Vclt8 Using laser scanners and high-tech computer software, Vince Rossi and Adam Metallo are recreating a digital Dinosaur Hall before it's dismantled

Almost 66 million years ago, an asteroid hit Earth – and changed our planet forever. From tsunamis to shockwaves, join us on a journey through time as we explore the science behind this cataclysmic event. READ MORE about the last day of a dinosaur here: https://www.smithsonianmag.com/science-nature/the-last-day-in-the-life-of-an-edmontosaurus-180979932/ --- For more videos from Smithsonian Magazine: https://www.smithsonianmag.com/videos/ Digital Editorial Director: Brian Wolly Supervising Producer & Scriptwriter: Michelle Mehrtens Video Editor: Sierra Theobald

The metropolis is an important center for paleontological research, but until now, fossils of plants and fish were the only remains of dinosaur-era life found there

The 237-million-year-old remains are among the oldest silesaurid fossils ever found, adding to paleontologists' understanding of this still-mysterious group of prehistoric reptiles

Ginoogaming First Nation has declared a state of emergency after an engineering inspection showed the bridge leading to the community should be closed to traffic.

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners