Katherine Binzel

Systemic Biodistribution and Intravitreal Pharmacokinetic Properties of Bevacizumab, Ranibizumab, and Aflibercept in a Nonhuman Primate Model

Purpose To determine the intravitreal pharmacokinetic properties and to study the systemic biodistribution characteristics of I-124-labeled bevacizumab, ranibizumab, and aflibercept with positron emission tomography-computed tomography (PET/CT) imaging in a nonhuman primate model. Methods Three groups with four owl monkeys per group underwent intravitreal injection with 1.25 mg/0.05 mL I-124 bevacizumab, 0.5 mg/0.05 mL I-124 ranibizumab, or 2.0 mg/0.05 mL I-124 aflibercept in the right eye of each subject. All subjects were imaged using PET/CT on days 0, 1, 2, 4, 8, 14, 21, 28, and 35. Serum blood draws were performed at hours 1, 2, 4, 8, 12 and days 1, 2, 4, 8, 14, 21, 28, and 35. Radioactivity emission measurements were used to determine the intravitreal half-lives of each agent and to study the differences of radioactivity uptake in nonocular organs. Results The intravitreal half-lives were 3.60 days for I-124 bevacizumab, 2.73 days for I-124 ranibizumab, and 2.44 days for I-124 aflibercept. Serum levels were highest and most prolonged for bevacizumab as compared to both ranibizumab and aflibercept. All agents were primarily excreted through the renal and mononuclear phagocyte systems. However, bevacizumab was also found in significantly higher levels in the liver, heart, and distal femur bones. Conclusions Among the three anti-VEGF agents used in clinical practice, bevacizumab demonstrated the longest intravitreal retention time and aflibercept the shortest. Significantly higher and prolonged levels of bevacizumab were found in the serum as well as in the heart, liver, and distal bones. These differences may be considered by clinicians when formulating treatment algorithms for intravitreal therapies with these agents.

Advanced Functional Tumor Imaging and Precision Nuclear Medicine Enabled by Digital PET Technologies

The purpose of this article is to provide a brief overview of the background, basic principles, technological evolution, clinical capabilities, and future directions for functional tumor imaging as PET evolves from the conventional photomultiplier tube-based platform into a fully digital detector acquisition platform. The recent introduction of solid-state digital photon counting PET detector is the latest evolution of clinical PET which enables faster time-of-flight timing resolution that leads to more precise localization of the annihilation events and further contributes to reduction in partial volume and thus makes high definition and ultrahigh definition PET imaging feasible with current standard acquisition procedures. The technological advances of digital PET can be further leveraged by optimizing many of the acquisition and reconstruction methodologies to achieve faster image acquisition to improve cancer patient throughput, lower patient dose in accordance with ALARA, and improved quantitative accuracy to enable biomarker capability. Digital PET technology will advance molecular imaging capabilities beyond oncology and enable Precision Nuclear Medicine.

ACL graft metabolic activity assessed by 18FDG PET–MRI

BACKGROUND To demonstrate the use of 18Fluorodeoxyglucose positron emission tomography (PET) and magnetic resonance imaging (MRI) in combination (18FDG-PET) to assess the metabolic activity of ACL graft tissue and evaluate the utility of this technique for ligament imaging. METHODS Twenty-one knees with intact ACL grafts in 19 patients at multiple time points following ACL reconstruction were recruited to participate. PET-MRI imaging was performed using a custom device to place knees in the same position for both studies. Images were co-registered for quantification of 18FDG-PET standardized uptake value (SUV) for the proximal, middle, and distal ACL was quantified. Signal in extra-articular muscle tissue in the index knee was also recorded as a control. Signal from each location was compared based on how far post-operative each knee was from ACL reconstruction (<6months, six to 12months, 12-24months, or >24months). RESULTS Significant differences in 18FDG PET SUV between the four time points were observed in the proximal (p=0.02), middle (p=0.004), and distal (p=0.007) portions of the ACL graft. The greater than 24months group was noted to be different from other groups in each case. No difference in PET 18FDG SUV was noted in the extra-articular muscle in the index knee in each time group (p=0.61). CONCLUSIONS Metabolic activity was noted to be significantly lower in grafts imaged greater than two years post-reconstruction relative to those grafts that had been in place for shorter periods of time.

90Y Digital PET/CT Imaging Following Radioembolization.

Imaging of Y internal pair production with conventional photomultiplier detector PET technology has been previously reported for patients with malignant/metastatic liver lesions treated with Y radioembolization (RE). We present a 54-year-old man with unresectable liver metastases from rectal carcinoma (involving the right and left lobes) who was referred for Y RE and subsequently imaged using new solid-state digital photon counting technology (Vereos 64 Time-of-Flight PET/CT; Philips, Cleveland, OH). Despite imaging at 26 hours following RE, digital PET/CT provides improved image quality and Y-to-background contrast as well as accurate visualization of Y biodistribution when compared with Bremsstrahlung SPECT/CT.