OBJECTIVE:This study aims to characterize and compare the saturation limits, spatial resolution, and image quality of various conventional and emerging positron-emitting radionuclides using a preclinical PET/CT scanner. By characterizing the performance of these radionuclides, the study sought to provide insights into their utility in high-resolution PET imaging. METHODS:Radionuclides (18F, 43Sc, 45Ti, 48V, 52Mn, 55Co, 64Cu, 68Ga, 89Zr) were evaluated on a GNEXT PET/CT scanner (Xodus Imaging, Torrance, CA) using saturation and Derenzo phantoms. Saturation was assessed by measuring the deviation between the actual and the region of interest (ROI) activity at varying concentrations of each radionuclide. Spatial resolution was quantified using full-width half maximum (FWHM) measurements from intensity profiles across six Derenzo phantom diameter sizes (1.2 mm-4.8 mm). Signal-to-noise ratios (SNRs) were calculated as a measure of image quality and Bland-Altman plots were used to assess the repeatability of resolution measurements. Statistical comparisons of test-retest were done to evaluate differences in accuracy and consistency across radionuclides. RESULTS:Saturation analysis revealed a broad range of limits across radionuclides, with 64Cu having the highest saturation threshold near 2 mCi (74 MBq), while 52Mn exhibited the lowest at approximately 250 μCi (9.25 MBq). Spatial resolution was inversely related to positron energy, with radionuclides like 18F and 64Cu producing clear images down to rod sizes of 1.6 mm compared to 68Ga and 55Co, which showed blurring at the same rod size. SNR analysis confirmed the superior image quality of lower-energy radionuclides, particularly for smaller structures, visually resolvable to 1.6 mm. Bland-Altman analysis showed that across the combination of rod sizes, 18F displayed improved repeatability in resolution measurements compared to 68Ga (standard errors of 0.03 and 0.15, respectively). CONCLUSION:This study demonstrates that the physical properties of radionuclides, particularly positron energy, significantly affected PET image quality, spatial resolution, and saturation thresholds. Lower-energy radionuclides like 18F and 52Mn are optimal for high-resolution applications, while higher energy radionuclides are better suited for high-activity imaging. These findings provide valuable guidance for optimizing radionuclide selection in preclinical and clinical PET imaging studies.

CD38 is an excellent biomarker and therapeutic target for multiple myeloma due to its high expression on cancerous cells in comparison to healthy cells. We aimed to adapt Isatuximab as a PET imaging agent to detect CD38 positive multiple myeloma. In vitro studies confirmed the specificity of [89Zr]Zr-DFO-Isatuximab in CD38 + OPM-2 and MM.1S cells. Upregulation of CD38 was performed using pomalidomide and ricolinostat. Athymic nude mice were implanted with OPM-2 tumors and PET/CT images were collected 24 h, 3d, and 7d post-injection. Dosimetry data was collected from male and female mice and calculated using OLINDA. Three productions of [89Zr]Zr-DFO-Isatuximab were produced using GMP techniques and validated for use in the clinic. Upregulation of CD38 was observed in vitro in CD38 + cells when treated with either pomalidomide or ricolinostat. In vivo evaluation of [89Zr]Zr-DFO-Isatuximab showed high selectivity in OPM-2 xenografts. Blocking with an excess of unlabeled Isatuximab reduced the tumor accumulation of [89Zr]Zr-DFO-Isatuximab by 45.5–48.5

Hands-on synthetic laboratory experiences are critically important for undergraduate chemistry majors. A senior undergraduate research experience at the College of Wooster is presented in the current work. The inorganic complexes [Cu(phenan)2(NO3)2 ] (1; phenan = phenanthridine) and [Au(phenan)Cl3](2) were prepared by metallation of the phenan ligand in a 1:1 CH3OH/CH2 Cl2 mixture at room temperature. Complex 1 is a new inorganic coordination compound. The structures were confirmed by X-ray crystallography. Complex 1 reveals a distorted octahedral geometry around the central Cu (II) metal ion. In complex 2 , the Au(III) atom exhibits a square planar geometry. In addition, we investigated [Cu(dmeobpy)(H2O)2][NO3]2 (3; dmeobpy = 4,4’-dimethoxy-2,2’-bipyridine), [Cu(bap)(NO3)2](4; bap = 2,6-bis(azaindole)pyridine) and [Re(CO)3(dmeobpy)Cl] (5). The cytoxocities of 1-5, phenan, dmeobpy, bap and cisplatin were evaluated against several human non-small cell lung cancer cell lines (NCI-H1975, HCC827, NCI-H460, and NCI-A549). Compound 1 exhibited modest antitumor activity against the HCC827 cell line, with an IC 50 value of 19 µM. Compound 3 exhibits lower cytotoxic activity than 1 . The cytotoxic activity of complex 5 ( IC50<11 µM) is significantly greater than 1 and 3 against the H1975 cancer cell line.

89Zr-labeled antibodies are being investigated in several clinical trials; however, the time requirement for synthesis of clinical doses can hinder patient throughput because of scheduling difficulties. Additionally, low specific activity due to poor labeling efficiency can require larger amounts of the radiopharmaceutical to be administered, possibly leading to adverse side effects. Here, we describe the design and evaluation of a microfluidic reactor capable of synthesizing a single clinical dose of 89Zr-labeled antibody. 89Zr-labeled trastuzumab was chosen for this validation because it is currently being evaluated in clinical trials for imaging human epidermal growth factor receptor 2–positive cancer patients. Methods: A microreactor fabricated from polydimethylsiloxane/glass was silanated with trimethoxy(octadecyl) silane to reduce antibody adsorption. Desferrioxamine-p-benzyl-isothiocyanate (DFO-Bz-NCS) was conjugated to trastuzumab in an 8:1 molar ratio following the literature procedures using aseptic techniques. Radiolabeling was performed by pumping 89Zr-oxalate and DFO-Bz-trastuzumab into the microfluidic reactor at a total rate of 20 μL/min in ratios varying from 1:37 to 1:592 mg:MBq at 37°C to achieve optimal labeling. Results: Silanated reactors showed low antibody adsorption in comparison to unmodified reactors (95% monoclonal antibody recovered vs. 0% recovered). Labeling of the modified trastuzumab was shown to be achievable at a specific activity above the reported literature value of 220 MBq/mg. A high radiochemical purity was achieved without an incubation period at specific activities of less than 148 MBq/mg; however, specific activities up to 592 MBq/mg could be achieved with an incubation period. Clinical doses were able to be prepared and passed all quality control guidelines set by the Food and Drug Administration. Samples were sterile, colorless, and radiochemically pure (100%); maintained the ability to bind to the intended receptor; formed a minimal amount of aggregates (1%–4%); and were completed within 45–60 min. Conclusion: 89Zr-labeled trastuzumab for use in a clinical setting was synthesized in a microfluidic reactor in under an hour while reducing the amount of handling required by a technician. Use of this compact platform not only could enable the use of radiolabeled antibodies to become a common practice, but also could spread the use of radiolabeled antibodies beyond locations with cyclotron facilities.

Irrespective of the order of the addition of reagents, the reactions of [PCl2N]3 with MX3 (MX3 = AlCl3, AlBr3, GaCl3) in the presence of water or gaseous HX give the air- and light-sensitive superacid adducts [PCl2N]3·HMX4. The reactions are quantitative when HX is used. These reactions illustrate a Lewis acid/Brønsted acid dichotomy in which Lewis acid chemistry can become Brønsted acid chemistry in the presence of adventitious water or HX. The crystal structures of all three [PCl2N]3·HMX4 adducts show that protonation weakens the two P-N bonds that flank the protonated nitrogen atom. Variable-temperature NMR studies indicate that exchange in solution occurs in [PCl2N]3·HMX4, even at lower temperatures than those for [PCl2N]3·MX3. The fragility of [PCl2N]3·HMX4 at or near room temperature and in the presence of light suggests that such adducts are not involved directly as intermediates in the high-temperature ring-opening polymerization (ROP) of [PCl2N]3 to give [PCl2N]n. Attempts to catalyze or initiate the ROP of [PCl2N]3 with the addition of [PCl2N]3·HMX4 at room temperature or at 70 °C were not successful.

The reactions of [PCl2N](3) with oxygen containing Lewis bases (OE) such as hexamethylphosphoramide (HMPA) and triethylphosphine oxide result in Cl/O exchange. The reactions occur via a two-step process which involves (1) formation of an intermediate salt [P3N3Cl5O](-)[E-Cl](+) and (2) attack by more OE to form P3N3Cl4O-OE and [E-Cl](+)[Cl](-). In addition to spectral characterizations, both phosphazene products of the HMPA reactions have been characterized by X-ray crystallography. As shown by reaction chemistry and the Gutmann-Beckett Lewis acidity scale, the PO of the phosphazene ring in P3N3Cl4O-OE has a strong Lewis acid character. We also discuss attempts to use other OE and more vigorous reaction conditions with the goal of preparing [PON](3) or its base-stabilized adducts. Such molecules could be precursors to novel PNO materials.

The purpose of the present study is to evaluate safety, human radiation dosimetry, and optimal imaging time of [89Zr]trastuzumab in patients with HER2-positive breast cancer.

The anti-tumor activity of imidazolium salts is highly dependent upon the substituents on the nitrogen atoms of the imidazolium cation. We have synthesized and characterized a series of naphthalene-substituted imidazolium salts and tested them against a variety of non-smallcell lung cancer cell lines. Several of these complexes displayed anticancer activity comparable to cisplatin. These compounds induced apoptosis in the NCI-H460 cell line as determined by Annexin V staining, caspase-3, and PARP cleavage. These results strongly suggest that this class of compounds can serve as potent chemotherapeutic agents.

Pertuzumab is a monoclonal antibody that binds to HER2 and is used in combination with another HER2–specific monoclonal antibody, trastuzumab, for the treatment of HER2+ metastatic breast cancer. Pertuzumab binds to an HER2 binding site distinct from that of trastuzumab, and its affinity is enhanced when trastuzumab is present. We aim to exploit this enhanced affinity of pertuzumab for its HER2 binding epitope and adapt this antibody as a PET imaging agent by radiolabeling with 89Zr to increase the sensitivity of HER2 detection in vivo. Here, we investigate the biodistribution of 89Zr-pertuzumab in HER2–expressing BT-474 and HER2–nonexpressing MDA-MB-231 xenografts to quantitatively assess HER2 expression in vivo. In vitro cell binding studies were performed resulting in retained immunoreactivity and specificity for HER2–expressing cells. In vivo evaluation of 89Zr-pertuzumab was conducted in severely combined immunodeficient mice, subcutaneously inoculated with BT-474 and MDA-MB-231 cells. 89Zr-pertuzumab was systemically administered and imaged at 7 days postinjection (p.i.) followed by terminal biodistribution studies. Higher tumor uptake was observed in BT-474 compared to MDA-MB-231 xenografts with 47.5 ± 32.9 and 9.5 ± 1.7% ID/g, respectively at 7 days p.i (P = 0.0009) and blocking studies with excess unlabeled pertuzumab showed a 5-fold decrease in BT-474 tumor uptake (P = 0.0006), confirming the in vivo specificity of this radiotracer. Importantly, we observed that the tumor accumulation of 89Zr-pertuzumab was increased in the presence of unlabeled trastuzumab, at 173 ± 74.5% ID/g (P = 0.01). Biodistribution studies correlate with PET imaging quantification using max SUV (r = 0.98, P = 0.01). Collectively, these results illustrate that 89Zr-pertuzumab as a PET imaging agent may be beneficial for the quantitative and noninvasive assessment of HER2 expression in vivo especially for patients undergoing trastuzumab therapy.

Medium-sized cyclic oligomeric phosphazenes [PCl2N]m (where m = 5-9) that were prepared from the reaction of PCl5 and NH4Cl in refluxing chlorobenzene have been isolated by a combination of sublimation/extraction and column chromatography from the predominant products [PCl2N]3 and [PCl2N]4. The medium-sized rings [PCl2N]m have been characterized by electrospray ionization-mass spectroscopy (ESI-MS), their (31)P chemical shifts have been reassigned, and their T1 relaxation times have been obtained. Crystallographic data has been recollected for [PCl2N]5, and the crystal structures of [PCl2N]6, and [PCl2N]8 are reported. Halogen-bonding interactions were observed in all the crystal structures of cyclic [PCl2N]m (m = 3-5, 6, 8). The crystal structures of [P(OPh)2N]7 and [P(OPh)2N]8, which are derivatives of the respective [PCl2N]m, are also reported. Comparisons of the intermolecular forces and torsion angles of [PCl2N]8 and [P(OPh)2N]8 with those of three other octameric rings are described. The comparisons show that chlorophosphazenes should not be considered prototypical, in terms of solid-state structure, because of the strong influence of halogen bonding.