Comparative biodistribution analysis across four different ⁸⁹Zr-monoclonal antibody tracers—The first step towards an imaging warehouse

Abstract

Rationale: Knowledge on monoclonal antibody biodistribution in healthy tissues in humans can support clinical drug development. Molecular imaging with positron emission tomography (PET) can yield information in this setting. However, recent imaging studies have analyzed the behavior of single antibodies only, neglecting comparison across different antibodies.Methods: We compared the distribution of four 89Zr-labeled antibodies in healthy tissue in a retrospective analysis based on the recently published harmonization protocol for 89Zr-tracers and our delineation protocol.Results: The biodistribution patterns of 89Zr-lumretuzumab, 89Zr-MMOT0530A, 89Zr-bevacizumab and 89Zr-trastuzumab on day 4 after tracer injection were largely similar. The highest tracer concentration was seen in healthy liver, spleen, kidney and intestines. About one-third of the injected tracer dose was found in the circulation, up to 15% in the liver and only 4% in the spleen and kidney. Lower tracer concentration was seen in bone marrow, lung, compact bone, muscle, fat and the brain. Despite low tracer accumulation per gram of tissue, large-volume tissues, especially fat, can influence overall distribution: On average, 5-7% of the injected tracer dose accumulated in fat, with a peak of 19% in a patient with morbid obesity.Conclusion: The similar biodistribution of the four antibodies is probably based on their similar molecular structure, binding characteristics and similar metabolic pathways. These data provide a basis for a prospectively growing, online accessible warehouse of molecular imaging data, which enables researchers to increase and exchange knowledge on whole body drug distribution and potentially supports drug development decisions.

Sub-cutaneous Fat Mass measured on multislice computed tomography of pretreatment PET/CT is a prognostic factor of stage IV non-small cell lung cancer treated by nivolumab

“…In a study exploring the biodistribution of four therapeutic antibodies (lumretuzumab, MMOT0530A, bevacizumab, and trastuzumab) labeled by radioactive 89 Zr, Bensch et al found that an estimated total amount of tracer accumulated in fat tissue ranged between 1.56% and 18.95% of the injected dose, depending on the physique of the patient. 27 A similar biodistribution was found for the four antibodies, probably because of their similar molecular structure, binding characteristics, and catabolic pathways. 27 Hence, despite low accumulation per gram of tissue, fat can influence the overall distribution of therapeutic antibodies.…”

“…27 A similar biodistribution was found for the four antibodies, probably because of their similar molecular structure, binding characteristics, and catabolic pathways. 27 Hence, despite low accumulation per gram of tissue, fat can influence the overall distribution of therapeutic antibodies. 27 This "storage effect" of the adipose tissue may contribute to our results.…”

New excitation functions measurement of nuclear reactions induced by deuteron beams on yttrium with particular reference to the production of 89Zr

“…Thanks to its nuclear characteristics (t 1/2 =78.41 h, 22.3% positron emission with a maximum decay energy of 900 keV), zirconium-89 ( 89 Zr) is a very promising radionuclide for immuno-PET (positron emission tomography using an antibody to target the cells of interest) [1][2][3][4][5]. It can also be used for bio distribution studies of labelled monoclonal antibodies [6]; furthermore, in literature it was reported a method to prepare pharmaceuticals for simultaneous magnetic resonance imaging and PET [7].…”

Vascular endothelial growth factor (VEGF) expression and neuroinflammation is increased in the frontopolar cortex of individuals with autism spectrum disorder

“…Given this caveat, we cautiously interpret our findings and encourage replication studies and those that examine VEGF-A levels in the brains of ASD patients in vivo . For example, the anti-VEGF antibody bevacizumab has been radiolabeled with zirconium-89 ( 89 Zr-bevacizumab) and used in clinical applications, showing some uptake into the brain [69,70]. However, the utility of 89 Zr-bevacizumab as an imaging marker capable of detecting modest changes in VEGF-A levels in the central nervous system is yet to be demonstrated.…”