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Ephrin type-A 2 (EphA2) is a transmembrane receptor expressed in epithelial cancers. We report on a phase I dose escalation and biodistribution study of DS-8895a, an anti-EphA2 antibody, in patients with advanced EphA2 positive cancers. DS-8895a was administered at 1, 3, 10 or 20 mg/kg every 2 weeks to determine safety, pharmacokinetics and anti-tumor efficacy. All patients underwent 89 Zr trace-labelled infusion of DS-8895a ( 89 Zr-DS-8995a) positron emission tomography imaging to determine the biodistribution of DS-8895a, and correlate findings with EphA2 expression, receptor saturation and response. Nine patients were enrolled on study. Of patients enrolled, seven patients received at least one infusion of DS-8895a: four patients received 1 mg/kg dose (Cohort 1) and three patients received 3 mg/kg dose (Cohort 2). Median age was 67.0 years (range 52-81), majority male (71%), and median number of prior systemic therapies was three (range 0-8). The primary cancer diagnosis was colorectal cancer (two patients) and one patient each had gastric, head and neck, high-grade serous adenocarcinoma, lung, and pancreatic cancers. No dose-limiting toxicities or treatment-related adverse events reported. The best response for the patients in Cohort 1 was stable disease and in Cohort 2 was progressive disease. 89 Zr-DS-8895a demonstrated no normal tissue uptake and specific low-grade uptake in most tumours. DS-8895a had limited therapeutic efficacy at doses evaluated and 89 Zr-DS-8895a demonstrated low tumour uptake. The biodistribution data from this study were key in halting further development of DS-8895a, highlighting the importance of biodistribution studies in drug development. (Trial registration: ClinicalTrials.gov Identifier NCT02252211)., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The scalable XCAT voxelised phantom was used with the GATE Monte Carlo toolkit to investigate the effect of voxel size on dosimetry estimates of internally distributed radionuclide calculated using direct Monte Carlo simulation. A uniformly distributed Fluorine-18 source was simulated in the Kidneys of the XCAT phantom with the organ self dose (kidney ← kidney) and organ cross dose (liver ← kidney) being calculated for a number of organ and voxel sizes. Patient specific dose factors (DF) from a clinically acquired FDG PET/CT study have also been calculated for kidney self dose and liver ← kidney cross dose. Using the XCAT phantom it was found that significantly small voxel sizes are required to achieve accurate calculation of organ self dose. It has also been used to show that a voxel size of 2 mm or less is suitable for accurate calculations of organ cross dose. To compensate for insufficient voxel sampling a correction factor is proposed. This correction factor is applied to the patient specific dose factors calculated with the native voxel size of the PET/CT study.

Purpose: To assess the contribution of concurrent low-dose, noncontrast CT in the assessment of the malignant potential of incidental focal 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-avid colonic lesions on positron emission tomography/computed tomography (PET/CT)., Procedures: Routine FDG-PET/CT scans were reviewed for identification of focal FDG-avid colon lesions, and the CT component was independently reviewed for an anatomical lesion and malignant potential based on CT criteria. Clinical, endoscopic, and histopathology follow-up was obtained., Results: A total of 85/2,916 (3%) oncology FDG-PET/CT scans had incidental focal colon lesions. Clinical and/or endoscopic follow-up was available in 83/85 (98%) patients. Focal, corresponding CT lesions were found in 44/83 (53%) patients, but features of malignancy were not assessable. Of the 44 patients with a final diagnosis, 32/44 (73%) were FDG-PET/CT true positives; 5/44 (11%) were false positives; and 7/44 (16%) had inconclusive FDG-PET/CT findings., Conclusions: Concurrent low-dose, noncontrast CT improves localization, but does not provide independent information on the malignant potential of incidental focal colonic activity on FDG-PET/CT.