Radiolabeling Diaminosarcophagine with Cyclotron-Produced Cobalt-55 and [55Co]Co-NT-Sarcage as a Proof of Concept in a Murine Xenograft Model.

Cobalt-sarcophagine complexes exhibit high kinetic inertness under various stringent conditions, but there is limited literature on radiolabeling and in vivo positron emission tomography (PET) imaging using no carrier added 55Co. To fill this gap, this study first investigates the radiolabeling of DiAmSar (DSar) with 55Co, followed by stability evaluation in human serum and EDTA, pharmacokinetics in mice, and a direct comparison with [55Co]CoCl2 to assess differences in pharmacokinetics. Furthermore, the radiolabeling process was successfully used to generate the NTSR1-targeted PET agent [55Co]Co-NT-Sarcage (a DSar-functionalized SR142948 derivative) and administered to HT29 tumor xenografted mice. The [55Co]Co-DSar complex can be formed at 37 °C with purity and stability suitable for preclinical in vivo radiopharmaceutical applications, and [55Co]Co-NT-Sarcage demonstrated prominent tumor uptake with a low background signal. In a direct comparison with [64Cu]Cu-NT-Sarcage, [55Co]Co-NT-Sarcage achieved a higher tumor-to-liver ratio but with overall similar biodistribution profile. These results demonstrate that Sar would be a promising chelator for constructing Co-based radiopharmaceuticals including 55Co for PET and 58mCo for therapeutic applications.

Excitation function of 54Fe(p,α)51Mn from 9.5 MeV to 18 MeV.

Excitation function of the 54Fe(p,α)51Mn reaction was measured from 9.5 to 18 MeV E 0 , p + by activating a foil stack of 54Fe electrodeposited on copper substrates. Residual radionuclides were quantified by HPGe gamma ray spectrometry. Both 51Mn (t 1/2 = 46.2 min, 〈 E ß + 〉 = 963.7 keV , I ß + = 97 % ; E γ = 749.1 keV, I γ = 0.265%) and its radioactive daughter, 51Cr (t 1/2 = 27.704d, E γ = 320.1 keV, I γ = 9.91%), were used to indirectly quantify formation of 51Mn. Results agree within uncertainty to the only other measurement in literature and predictions of default TALYS theoretical code. Final relative uncertainties are within ±12%.

Addressing the challenges of reoperative robotic-assisted sacrocolpopexy.

Sacrocolpopexy is the gold-standard repair for apical pelvic organ prolapse (POP). However, over half of women with POP who undergo the surgery experience recurrence, particularly those with higher preoperative stage, younger age, and greater body weight. We address the challenges of repairing recurrent POP in a patient with a prior transabdominal mesh sacrohysteropexy.

Anatomic Reasons for Failure to Visualize the Appendix With Graded Compression Sonography: Insights From Contemporaneous CT.

OBJECTIVE: The purpose of this study is to identify the anatomic locations of appendixes on CT when graded compression sonography fails to visualize the appendix. MATERIALS AND METHODS: The study included 197 patients with suspected appendicitis whose appendixes were not visualized on graded compression sonography performed with typically used transducers of at least 10 MHz, who underwent CT within 48 hours following graded compression sonography, and who had available either pathologic examination following surgery or 6-week follow-up if surgery was not performed. Appendixes were retrospectively localized using four transverse quadrants (including the posteromedial quadrant) centered on the ileocecal valve and projected vertically, the craniocaudal level relative to the iliac crests, and the depth of the appendix as measured from the surface of the skin. Data were assessed using the Fisher exact test, t test, multinomial test, binomial distribution, ANOVA, and linear regression. RESULTS: Appendixes were most frequently located in the posteromedial quadrant (123 of 197 patients [62.4%]; 95% CI, 55.3-69.2%) at a statistically significantly greater frequency than that expected by chance (p < 0.00001). Appendixes were located above the iliac crests in 19.8% of patients (39/197; 95% CI, 14.5-26.1%) and at depths exceeding the penetration of typical transducers of at least 10 MHz in 19.3% of patients (38/197; 95% CI, 14.0-25.5%). All appendixes (95% CI, 98.1-100.0%) were located within the range of 6-MHz transducers. CONCLUSION: Appendixes that are not visualized on graded compression sonography are most frequently located in the posteromedial quadrant and are often located above the iliac crests or at depths too great for visualization with typically used transducers of at least 10 MHz. Accordingly, when the appendix is not visualized on graded compression sonography, targeted scanning of the posteromedial quadrant and the region above the iliac crests, and scanning with 6-MHz transducers, may enable visualization of the appendix and are recommended additions to scanning protocols.

Noninvasive PET imaging of tumor PD-L1 expression with 64Cu-labeled Durvalumab.

Breast cancer (BrCa) ranks as the most prevalent malignant neoplasm affecting women worldwide. The expression of programmed death-ligand 1 (PD-L1) in BrCa has recently emerged as a biomarker for immunotherapy response, but traditional immunohistochemistry (IHC)-based methods are hindered by spatial and temporal heterogeneity. Noninvasive and quantitative PD-L1 imaging using appropriate radiotracers can serve to determine PD-L1 expression in tumors. This study aims to demonstrate the viability of PET imaging with 64Cu-labeled Durvalumab (abbreviated as Durva) to assess PD-L1 expression using a murine xenograft model of breast cancer. Durvalumab, a human IgG1 monoclonal antibody against PD-L1, was assessed for specificity in vitro in two cancer cell lines (MDA-MB-231 triple-negative breast cancer cell line and AsPC-1 pancreatic cancer cell line) with positive and negative PD-L1 expression by flow cytometry. Next, we performed the in vivo evaluation of 64Cu-NOTA-Durva in murine models of human breast cancer by PET imaging and ex vivo biodistribution. Additionally, mice bearing AsPC-1 tumors were employed as a negative control. Tumor uptake was quantified based on a 3D region-of-interest (ROI) analysis of the PET images and ex vivo biodistribution measurements, and the results were compared against conventional IHC testing. The radiotracer uptake was evident in MDA-MB-231 tumors and showed minimal nonspecific binding, corroborating IHC-derived results. The results of the biodistribution showed that the MDA-MB-231 tumor uptake of 64Cu-NOTA-Durva was much higher than 64Cu-NOTA-IgG (a nonspecific radiolabeled IgG). In Conclusion, 64Cu-labeled Durvalumab PET/CT imaging offers a promising, noninvasive approach to evaluate tumor PD-L1 expression.

Biparametric versus multiparametric MRI for the detection of clinically significant prostate cancer in a diverse, multiethnic population.

PURPOSE: There is not yet satisfactory performance data comparing multiparametric MRI (mpMRI) versus biparametric MRI (bpMRI) for detecting prostate cancer (PCa), particularly in high-risk populations. We compared both protocols for detecting overall PCa and clinically significant PCa (CS-PCa; defined as Grade Group ≥ 2) in a multiethnic urban population. METHODS: We retrospectively reviewed electronic medical record data from men who underwent image-guided fusion prostate biopsy (FB) between 2016 and 2021 at our institution. Patient characteristics, Prostate Imaging Reporting and Data System (PI-RADS) scores, and FB outcomes were analyzed based on MRI protocol. Multivariate mixed-effects logistic regression models were used to examine associations of bpMRI versus mpMRI for detecting overall PCa and CS-PCa in targeted lesions, among all patients and stratified by race/ethnicity. RESULTS: Overall, 566 men (44.0% Non-Hispanic Black [NHB]; 27.0% Hispanic) with 975 PI-RADS 3-5 lesions on MRI underwent FB. Of these, 312 (55%) men with 497 lesions underwent mpMRI and 254 (45%) men with 478 lesions underwent bpMRI. On multivariate analyses among all men, the odds of detecting overall PCa (OR = 1.18, 95% CI: 1.05-3.11, p = 0.031) and CS-PCa (OR = 2.15, 95% CI: 1.16-4.00, p = 0.014) on FB were higher for lesions identified on bpMRI than mpMRI. When stratified by race/ethnicity, the odds of detecting overall PCa (OR = 1.86; p = 0.15) and CS-PCa (OR = 2.20; p = 0.06) were not statistically different between lesions detected on bpMRI or mpMRI. CONCLUSION: BpMRI has similar diagnostic performance to mpMRI in detecting overall and CS-PCa within a racially/ethnically diverse population. BpMRI can be utilized for evaluating suspected CS-PCa among NHB and Hispanic men.

Synthesis of 64Cu-, 55Co-, and 68Ga-Labeled Radiopharmaceuticals Targeting Neurotensin Receptor-1 for Theranostics: Adjusting In Vivo Distribution Using Multiamine Macrocycles.

The development of theranostic radiotracers relies on their binding to specific molecular markers of a particular disease and the use of corresponding radiopharmaceutical pairs thereafter. This study reports the use of multiamine macrocyclic moieties (MAs), as linkers or chelators, in tracers targeting the neurotensin receptor-1 (NTSR-1). The goal is to achieve elevated tumor uptake, minimal background interference, and prolonged tumor retention in NTSR-1-positive tumors. Methods: We synthesized a series of neurotensin antagonists bearing MA linkers and metal chelators. The MA unit is hypothesized to establish a strong interaction with the cell membrane, and the addition of a second chelator may enhance water solubility, consequently reducing liver uptake. Small-animal PET/CT imaging of [64Cu]Cu-DOTA-SR-3MA, [64Cu]Cu-NT-CB-NOTA, [68Ga]Ga-NT-CB-NOTA, [64Cu]Cu-NT-CB-DOTA, and [64Cu]Cu-NT-Sarcage was acquired at 1, 4, 24, and 48 h after injection using H1299 tumor models. [55Co]Co-NT-CB-NOTA was also tested in HT29 (high NTSR-1 expression) and Caco2 (low NTSR-1 expression) colorectal adenocarcinoma tumor models. Saturation binding assay and internalization of [55Co]Co-NT-CB-NOTA were used to test tracer specificity and internalization in HT29 cells. Results: In vivo PET imaging with [64Cu]Cu-NT-CB-NOTA, [68Ga]Ga-NT-CB-NOTA, and [55Co]Co-NT-CB-NOTA revealed high tumor uptake, high tumor-to-background contrast, and sustained tumor retention (≤48 h after injection) in NTSR-1-positive tumors. Tumor uptake of [64Cu]Cu-NT-CB-NOTA remained at 76.9% at 48 h after injection compared with uptake 1 h after injection in H1299 tumor models, and [55Co]Co-NT-CB-NOTA was retained at 60.2% at 24 h compared with uptake 1 h after injection in HT29 tumor models. [64Cu]Cu-NT-Sarcage also showed high tumor uptake with low background and high tumor retention 48 h after injection Conclusion: Tumor uptake and pharmacokinetic properties of NTSR-1-targeting radiopharmaceuticals were greatly improved when attached with different nitrogen-containing macrocyclic moieties. The study results suggest that NT-CB-NOTA labeled with either 64Cu/67Cu, 55Co/58mCo, or 68Ga (effect of 177Lu in tumor to be determined in future studies) and NT-Sarcage labeled with 64Cu/67Cu or 55Co/58mCo may be excellent diagnostic and therapeutic radiopharmaceuticals targeting NTSR-1-positive cancers. Also, the introduction of MA units to other ligands is warranted in future studies to test the generality of this approach.

Visible-light-mediated Diels-Alder reactions under single-chain polymer confinement: investigating the role of the crosslinking moiety on catalyst activity.

Macromolecular scaffolds are rapidly emerging in catalysis owing to the ability to control catalyst placement at precise locations. This spatial proximity allows for enhanced catalyst activity that may not be observed using small molecules. Herein, we describe a triphenylpyrylium (TPT)-based visible-light active single-chain polymer nanoparticle (SCNP) that facilitates the radical cation [4 + 2]-cycloaddition. We find that the catalytic activity is highly dependent on the styrylarene comonomer used, wherein it can act as a redox mediator under confinement, increasing the catalytic turnover (TON) by up to 30 times in comparison to free TPT in solution. Mechanistic studies indicate that TPT excited states are quenched by the acene, with the resultant radical cation formed from naphthalene-based SCNPs able to proceed in oxidizing the dienophile in the elementary step of the reaction, while leading to near quantitative yields of the cycloadduct. The TPT-SCNP demonstrates enhanced photocatalyst efficiency compared to molecular TPT, and is able to be recycled and reused in three iterations of the reaction prior to decreased performance from photobleaching. Our results overall suggest that the confined nature of the SCNP and spatial proximity of acene-based pendants enforces their participation as cocatalytic redox mediators that impart enhanced photoredox catalysis under confinement.

Preclinical development of novel PD-L1 tracers and first-in-human study of [68Ga]Ga-NOTA-RW102 in patients with lung cancers.

BACKGROUND: The programmed cell death protein-1 (PD-1)/programmed death receptor ligand 1 (PD-L1) axis critically facilitates cancer cells' immune evasion. Antibody therapeutics targeting the PD-1/PD-L1 axis have shown remarkable efficacy in various tumors. Immuno-positron emission tomography (ImmunoPET) imaging of PD-L1 expression may help reshape solid tumors' immunotherapy landscape. METHODS: By immunizing an alpaca with recombinant human PD-L1, three clones of the variable domain of the heavy chain of heavy-chain only antibody (VHH) were screened, and RW102 with high binding affinity was selected for further studies. ABDRW102, a VHH derivative, was further engineered by fusing RW102 with the albumin binder ABD035. Based on the two targeting vectors, four PD-L1-specific tracers ([68Ga]Ga-NOTA-RW102, [68Ga]Ga-NOTA-ABDRW102, [64Cu]Cu-NOTA-ABDRW102, and [89Zr]Zr-DFO-ABDRW102) with different circulation times were developed. The diagnostic efficacies were thoroughly evaluated in preclinical solid tumor models, followed by a first-in-human translational investigation of [68Ga]Ga-NOTA-RW102 in patients with non-small cell lung cancer (NSCLC). RESULTS: While RW102 has a high binding affinity to PD-L1 with an excellent KD value of 15.29 pM, ABDRW102 simultaneously binds to human PD-L1 and human serum albumin with an excellent KD value of 3.71 pM and 3.38 pM, respectively. Radiotracers derived from RW102 and ABDRW102 have different in vivo circulation times. In preclinical studies, [68Ga]Ga-NOTA-RW102 immunoPET imaging allowed same-day annotation of differential PD-L1 expression with specificity, while [64Cu]Cu-NOTA-ABDRW102 and [89Zr]Zr-DFO-ABDRW102 enabled longitudinal visualization of PD-L1. More importantly, a pilot clinical trial shows the safety and diagnostic value of [68Ga]Ga-NOTA-RW102 immunoPET imaging in patients with NSCLCs and its potential to predict immune-related adverse effects following PD-L1-targeted immunotherapies. CONCLUSIONS: We developed and validated a series of PD-L1-targeted tracers. Initial preclinical and clinical evidence indicates that immunoPET imaging with [68Ga]Ga-NOTA-RW102 holds promise in visualizing differential PD-L1 expression, selecting patients for PD-L1-targeted immunotherapies, and monitoring immune-related adverse effects in patients receiving PD-L1-targeted treatments. TRIAL REGISTRATION NUMBER: NCT06165874.

The impact of computed tomography on early glottic cancer outcomes.

PURPOSE: Aim of this study was to evaluate the impact of computed tomography (CT)-based simulation and planning on early glottic cancer outcomes and toxicity. METHODS: This is a single-institution retrospective study of 253 patients with T1-2 glottic cancer who underwent radiation therapy (RT) from January 1998-2010. Group A (80%) underwent 2-dimensional RT (2DRT) and group B (20%) 3-dimensional RT (3DRT). 76% of patients in group A and 84% in group B had T1 cancer. The median dose and fraction size were 63 Gy and 2.25 Gy, respectively. RESULTS: With a median follow-up of 83, 93, and 30 months for the whole cohort, group A and B, respectively, the loco-regional control (LRC) was 97.6%. The rate of LRC for T1 disease was 99.5% and for T2 disease 91%. According to the RT modality, rates of LRC were 99.4 and 100% in groups A and B for T1, and 89.8 and 100% for T2. Long-term toxicity was negligible in both groups. Kaplan-Meier Curve showed the 5-year cause-specific survival to be 100%. Chi-square and multivariate analysis tests showed a significant relationship between CT simulation (3DRT) and LRC (p < 0.0001). CONCLUSION: CT-based simulation and planning provided better LRC and less acute side effects compared to 2DRT.

Separation of cyclotron-produced cobalt-55/58m from iron targets using cation exchange chromatography with non-aqueous solvents and extraction chromatography.

Cobalt-55 and -58m form a theranostic pair that has relevant properties for cancer research. We report a cation exchange chromatography/extraction chromatography method that separates cyclotron-produced 55/58mCo from 54/57Fe in <1.5 h, recovers >85% Co and achieves [55Co]Co-NOTA and -DOTA AMA 89 ± 48 and 35 ± 7 MBq/nmol (EOB), respectively. Cobalt-55 and -58m were quantitatively labeled to functionalized NOTA at 106 and 50 MBq/nmol (EOB), respectively, corroborating measured AMA. This method is faster than previously published methods and achieves better [55/58mCo]Co-NOTA and -DOTA AMA.

Theranostic cobalt-55/58m for neurotensin receptor-mediated radiotherapy in vivo: A pilot study with dosimetry.

Neurotensin receptor 1 (NTSR1) can stimulate tumor proliferation through neurotensin (NTS) activation and are overexpressed by a variety of cancers. The high binding affinity of NTS/NTSR1 makes radiolabeled NTS derivatives interesting for cancer diagnosis and staging. Internalization of NTS/NTSR1 also suggests therapeutic application with high LET alpha particles and low energy electrons. We investigated the therapeutic efficacy of [58mCo]Co-NOTA-NT-20.3 in vivo using murine models xenografted with NTSR1-positive HT29 human colorectal adenocarcinoma cells, and utilized [55Co]Co-NOTA-NT-20.3 for dosimetry. METHODS: Targeting properties and cytotoxicity of [55/58mCo]Co-NOTA-NT-20.3 were assessed with HT29 cells. Female nude mice were xenografted with HT29 tumors and administered [55Co or 58mCo]Co-NOTA-NT-20.3 to evaluate pharmacokinetics or for therapy, respectively. Dosimetry calculations followed the Medical Internal Radiation Dose (MIRD) formalism and human absorbed dose rate per unit activity were obtained from OpenDose. The pilot therapy study consisted of two groups (each N = 3) receiving 110 ± 15 MBq and 26 ± 6 MBq [58mCo]Co-NOTA-NT-20.3 one week after tumor inoculation, and control (N = 3). Tumor sizes and masses were measured twice a week after therapy. Complete blood count and kidney histology were also performed to assess toxicity. RESULTS: HPLC measured radiochemical purity of [55,58mCo]Co-NOTA-NT-20.3 > 99 %. Labeled compounds retained NTS targeting properties. [58mCo]Co-NOTA-NT-20.3 exhibited cytotoxicity for HT29 cells and was >15× more potent than [58mCo]CoCl2. Xenografted tumors responded modestly to administered doses, but mice showed no signs of radiotoxicity. Absorbed dose to tumor and kidney with 110 MBq [58mCo]Co-NOTA-NT-20.3 were 0.6 Gy and 0.8 Gy, respectively, and other organs received less than half of the absorbed dose to tumor. Off-target radiation dose from cobalt-58g was small but reduces the therapeutic window. CONCLUSION: The enhanced in vitro cytotoxicity and high tumor-to-background led us to investigate the therapeutic efficacy of [58mCo]Co-NOTA-NT-20.3 in vivo. Although we were unable to induce tumor response commensurate with [177Lu]Lu-NT127 (NLys-Lys-Pro-Tyr-Tle-Leu) studies involving similar time-integrated activity, the absence of observed toxicity may constitute an opportunity for targeting vectors with improved uptake and/or retention to avoid the aftereffects of other high-LET radioactive emissions. Future studies with higher uptake, activity and/or multiple dosing regimens are warranted. The theranostic approach employed in this work was crucial for dosimetry analysis.

Patient Perceptions of Video Visits in a Fee-for-Service Model.

INTRODUCTION: We studied perceptions of patients who receive telemedicine services in the fee-for-service setting of an academic medical center's family medicine department. To the best of our knowledge, this study is the first to investigate patient sentiments on both experiential and financial aspects of telemedicine primary care with copayment collection. METHODS: A 53-question cross-sectional digital survey was delivered to patients' e-mail addresses after their telemedicine visit. We tabulated summary statistics and performed 2-sample t-tests to compare survey responses across groups. RESULTS: Of 3,414 potential respondents, 903 responded, corresponding to a 26.7% effective response rate; 797 completed surveys were analyzed. Of these, 91% described their video visit experience as more convenient than office-based care, 74% reported shorter wait times, 87% felt confident about protection of privacy, 29% perceived copayments to be unreasonable, and 91% are willing to use telemedicine again. DISCUSSION: Our findings suggest that telemedicine is a viable alternative to in-person visits and that most patients find a copayment reasonable. The findings suggest that telemedicine offers convenience and consistency with continuity and corroborate previous studies investigating telemedicine viewpoints. Payors should consider copayment in detail when designing telehealth benefits to ensure they do not become a barrier in seeking care.

PET Imaging of the Neurotensin Targeting Peptide NOTA-NT-20.3 Using Cobalt-55, Copper-64 and Gallium-68.

Introduction: Neurotensin receptor 1 (NTSR1) is an emerging target for imaging and therapy of many types of cancer. Nuclear imaging of NTSR1 allows for noninvasive assessment of the receptor levels of NTSR1 on the primary tumor, as well as potential metastases. This work focuses on a the neurotensin peptide analogue NT-20.3 conjugated to the chelator NOTA for radiolabeling for use in noninvasive positron emission tomography (PET). NOTA-NT-20.3 was radiolabeled with gallium-68, copper-64, and cobalt-55 to determine the effect that modification of the radiometal has on imaging and potential therapeutic properties of NOTA-NT-20.3. Methods: In vitro assays investigating cell uptake and subcellular localization of the radiolabeled peptides were performed using human colorectal adenocarcinoma HT29 cells. In vivo PET/CT imaging was used to determine the distribution and clearance of the peptide in mice bearing NTSR1 expressing HT29 tumors. Results: Cell uptake studies showed that the highest uptake was obtained with [55Co] Co-NOTA-NT-20.3 (18.70 ± 1.30%ID/mg), followed by [64Cu] Cu-NOTA-NT-20.3 (15.46 ± 0.91%ID/mg), and lastly [68Ga] Ga-NOTA-NT-20.3 (10.94 ± 0.46%ID/mg) (p < 0.001). Subcellular distribution was similar across the three constructs, with the membranous fraction containing the highest amount of radioactivity. In vivo PET/CT imaging of the three constructs revealed similar distribution and tumor uptake at the 1 h imaging timepoint. Tumor uptake was receptor-specific and blockable by co-injection of non-radiolabeled NOTA-NT-20.3. SUV ratios of tumor to heart at the 24 h imaging timepoint show that [55Co] Co-NOTA-NT-20.3 (20.28 ± 3.04) outperformed [64Cu] Cu-NOTA-NT-20.3 (6.52 ± 1.97). In conclusion, our studies show that enhanced cell uptake and increasing tumor to blood ratios over time displayed the superiority of [55Co] Co-NOTA-NT-20.3 over [68Ga] Ga-NOTA-NT-20.3 and [64Cu] Cu-NOTA-NT-20.3 for the targeting of NTSR1.

Open-Shell Nanosensitizers for Glutathione Responsive Cancer Sonodynamic Therapy.

Deleterious effects to normal tissues and short biological half-life of sonosensitizers limit the applications of sonodynamic therapy (SDT). Herein, a new sonosensitizer (Cu(II)NS) is synthesized that consists of porphyrins, chelated Cu2+ , and poly(ethylene glycol) (PEG) to overcome the challenges of SDT. As Cu2+ contains 27 electrons, Cu(II)NS has an unpaired electron (open shell), resulting in a doublet ground state and little sonosensitivity. Overexpressed glutathione in the tumor can reduce Cu2+ to generate Cu(I)NS, leading to a singlet ground state and recuperative sonosensitivity. Additionally, PEG endows Cu(II)NS with increased blood biological half-life and enhanced tumor accumulation, further increasing the effect of SDT. Through regulating the valence state of Cu, cancer SDT with enhanced therapeutic index is achieved.

Production, Purification, and Applications of a Potential Theranostic Pair: Cobalt-55 and Cobalt-58m.

The emerging success of [68Ga/177Lu]Ga/Lu-DOTATATE as a theranostic pair has spurred interest in other isotopes as potential theranostic combinations. Here, we review cobalt-55 and cobalt-58m as a potential theranostic pair. Radionuclidically pure cobalt-55 and cobalt-58m have been produced on small cyclotrons with high molar activity. In vitro, DOTATOC labeled with cobalt has shown greater affinity for SSTR2 than DOTATOC labeled with gallium and yttrium. Similarly, [58mCo]Co-DOTATATE has shown improved cell-killing capabilities as compared to DOTATATE labeled with either indium-111 or lutetium-177. Finally, PET imaging with an isotope such as cobalt-55 allows for image acquisition at much later timepoints than gallium, allowing for an increased degree of biological clearance of non-bound radiotracer. We discuss the accelerator targetry and radiochemistry used to produce cobalt-55,58m, emphasizing the implications of these techniques to downstream radiotracers being developed for imaging and therapy.

Use of beta-blocker types and risk of incident prostate cancer in a multiethnic population.

PURPOSE: Increased adrenergic innervation is observed in prostate cancer (CaP) and is associated with aggressive disease. Emerging evidence suggests that beta-adrenergic blockade inhibits CaP progression. However, the association between type of beta-blocker use and risk of incident CaP on initial prostate biopsy has not been investigated in multiethnic populations. MATERIALS AND METHODS: A retrospective study of racially/ethnically diverse men (64% African-American and Hispanic), who underwent initial prostate biopsy between 2006 and 2016 in a large healthcare system was performed. Oral use of beta-blocker type was assessed by reviewing active prescriptions within the 5-year period preceding initial biopsy. Patient demographics and clinical factors were collected. RESULTS: Of 4,607 men who underwent initial prostate biopsy, 4,516 met criteria and 2,128 had a biopsy positive for CaP; 20% high-risk, 41% intermediate-risk, and 39% low or very-low risk (National Comprehensive Cancer Network classification). Overall, 15% of patients were taking a beta-blocker prior to initial biopsy, with Metoprolol, Atenolol, and Carvedilol accounting for the majority. Of beta-blocker types, Atenolol alone was associated with a 38% reduction in odds of incident CaP (P= 0.01), with a 40% and 54% reduction in risks of National Comprehensive Cancer Network intermediate and high-risk CaP (P = 0.03 and P = 0.03, respectively) compared to men not taking a beta-blocker. Furthermore, longer duration of Atenolol use (3-5 years) was associated with a 54% and 72% reduction in intermediate and high-risk disease, (P = 0.03 and P = 0.03, respectively). CONCLUSIONS: Among beta blocker types, long-term Atenolol use is associated with a significant reduction in incident CaP risk on initial prostate biopsy for clinically-significant intermediate and high-risk disease compared to men not taking a beta-blocker.

Non-Familial Synchronous Bilateral Renal Cell Carcinoma with Bilateral Synchronous Renal Vein Extension and Inferior Vena Cava Thrombus.

Bilateral renal cell carcinoma with tumor thrombus extension into the renal vein and/or inferior vena cava - clinical stage T3a+ - is rare. The majority of these cases arise due to a genetic predisposition. We present a case report of a 47-year-old male with bilateral, synchronous renal cell carcinoma with bilateral renal vein and inferior vena cava tumor thrombi with no identifiable familial predisposition.

Baseline chronic kidney disease does not predict long-term renal functional decline after percutaneous nephrolithotomy.

To compare renal functional outcomes in patients with and without chronic kidney disease (CKD) to identify predictors of change in renal function after percutaneous nephrolithotomy (PCNL). We reviewed patients who underwent PCNL by a single surgeon over 3.5 years. Patients' pre- and post-operative Glomerular Filtration Rate (GFR) was calculated. Baseline GFR < 60 ml/min/1.73 m2 (stage ≥ 3 CKD) defined our CKD cohort. Patients' baseline renal function, comorbidities, stone parameters, and intra-operative variables were analyzed to determine the relationship with post-operative renal function after PCNL by multivariate analysis. 202 patients were analyzed. Mean follow-up time was 16 months. At baseline, 163 (80.7%) patients were free of CKD and 39 (19.3%) had CKD. Patients without CKD had an overall decrease in GFR from 105.6 to 103.3 ml/min/1.73 m2 (p = 0.494). 14/163 (8.6%) non-CKD patients experienced a significant decline in renal function after PCNL; 7/163 (4.3%) developed de novo CKD and 7 had a ≥ 30% decline in GFR. Patients with CKD had an overall increase in mean GFR post-operatively, from 47.3 to 54.0 ml/min/m2 (p = 0.067). Two in this cohort (5.1%) experienced a > 30% decline in renal function post-operatively. Age, gender, African American race, presence of comorbidities and pre-operative CKD were not significant predictors of renal function post-operatively on multivariate analysis. PCNL in this cohort appears GFR neutral in the setting of baseline CKD. CKD was not predictive of renal functional decline after PCNL. Given that stone disease carries a high recurrence rate and that CKD is associated with stone formers, further investigation into predictors of renal function change after PCNL is warranted.

Low rates of contralateral neck failure in unilaterally treated oropharyngeal squamous cell carcinoma with prospectively defined criteria of lateralization.

BACKGROUND: Unilateral radiotherapy (RT) of oropharyngeal carcinomas is accepted for patients with lateralized primary and low-volume nodal disease. Utilizing prospectively defined criteria of laterality and staging positron emission tomography (PET)/CT, we studied outcomes in patients with advanced-stage oropharyngeal cancer undergoing unilateral RT. METHODS: Thirty-seven patients with oropharyngeal tumors >1 cm from midline regardless of node status underwent unilateral RT and were followed prospectively. Patient characteristics: T1 = 11; T2 = 22; T3 = 4; N0 = 3; N1 = 9; N2a = 3; N2b = 21; and Nx = 1. Dosimetry were determined and weekly National Comprehensive Cancer Network (NCCN) distress thermometer data were collected. RESULTS: At median follow-up of 32 months, 3-year locoregional control, contralateral regional failure, distant metastasis-free survival, and disease-free survival were 96%, 0%, 7%, and 93%, respectively. CONCLUSION: Low rates of contralateral neck failure are demonstrated utilizing prospectively defined criteria for unilateral RT. The tolerances of contralateral organs are respected and patients report low to moderate levels of distress throughout treatment.