Preclinical Characterization of 86/90Y-NM600 in a Variety of Murine and Human Cancer Tumor Models.

We characterize the in vivo biodistribution and tumor selectivity of 86Y-NM600, a theranostic alkylphosphocholine radiometal chelate with broad tumor selectivity, in a variety of preclinical cancer models. Methods: Mice bearing flank tumors (representative of lung, pancreatic, prostate, liver, skin, and lymphoid cancers) were injected intravenously with 9.25 MBq of 86Y-NM600 and imaged longitudinally over 4-5 d using small-animal PET/CT. Percentage injected activity per gram (%IA/g) for each volume of interest was measured at each time point for the organs of interest. Mice were euthanized after the final time point, and the tumor and organs of interest were counted with an automatic γ-counter. Absorbed doses delivered by 90Y-NM600 per injected activity (Gy/MBq) were estimated. Mice bearing B78 flank tumors were injected with a prescription of 90Y-NM600 that delivered 2.5 Gy of absorbed tumor dose and was compared with an equivalent absorbed dose delivered via external-beam radiotherapy using tumor volume as a measure of response. Histology and complete blood counts were analyzed in naïve C57BL/6 mice that were injected with 9.25 MBq of 90Y-NM600 at 5, 10, and 28 d after injection. Results: PET imaging showed consistent tumor accumulation and retention across all tumor models investigated, with little off-target retention of NM600 except in the liver, as is characteristic of hepatobiliary metabolism. The tumor uptake was highest in the pancreatic and lymphoid cancer models, reaching peak concentrations of 9.34 ± 2.66 %IA/g (n = 3) and 9.10 ± 0.13 %IA/g (n = 3), respectively, at approximately 40-48 h after injection. These corresponded to tumor dose estimates of 2.72 ± 0.33 Gy/MBq and 2.67 ± 0.32 Gy/MBq, respectively. In the toxicity study, there were no visible signs of acute toxicity by histology, and perturbation of hematologic parameters was transient when observed, returning to pretherapy levels after 28 d. Conclusion: NM600 is a theranostic agent with a unique ability to selectively target a variety of cancer types, presenting a unique opportunity for PET image-guided targeted radionuclide therapy and combination with immunotherapies.

Is all asthenopia the same?

PURPOSE: Any of several conditions can cause asthenopia. The purpose of this study was to determine whether the particular sensations or their location vary dependent on the symptom-inducing condition. METHODS: Twenty subjects with good vision performed eight reading tasks in random order during different conditions. Each condition used different stimuli to induce asthenopia. The eight conditions were mixed astigmatism, close viewing distance, upward gaze, dry eyes, lens flipper, small font, glare, and flickering light. Subjects were asked to read until attaining a level of discomfort self-defined as "barely tolerable." After each task, subjects rated the magnitude of several symptom descriptors (burning, ache, strain, irritation, tearing, blurred vision, double vision, dryness, and headache) and their location. RESULTS: Analysis of variance with repeated measures was used to determine that all of the individual symptom sensation measures (except blur) were significantly related (p values ranged from 0.003 to <0.0001) to the inducing condition. Principal factor analysis with orthogonal varimax rotation was used to test symptom by condition relationships and determined two latent factors, designated external and internal symptom factors (ESF and ISF), that related symptoms to inducing condition. The ESF pattern comprises burning, irritation, tearing, and dryness located in the front and bottom of the eye. ESF is caused by holding the eyelid open, glare, up gaze, small font, and flickering. ESF seems highly related to dry-eye symptoms. The ISF pattern comprises ache, strain, and headache located behind the eyes. ISF is caused by the close viewing distance, lens flipper, and mixed astigmatism conditions and is likely related to accommodative and vergence stress. CONCLUSIONS: Symptom descriptors and locations were able to distinguish discomfort on the basis of causative condition. Results support two different symptom constellations and, hence, at least two different afferent pathways for symptoms of asthenopia.