Arsenic PET imaging

When most people think of PET imaging, the more commonly used isotopes of ¹⁸F, ¹¹C, ¹⁵O and ⁸²Rb usually come to mind. When this article on arsenic imaging (free registration required I think) showed up in my feed reader a few days ago, I was a little intrigued. It certainly wouldn’t be the first time a toxic metal was used for imaging purposes. ²⁰¹Tl has been used as a cardiac imaging agent for years and is still used in a lot of places. Fortunately, the amounts used are way below toxicity levels making it safe to use for imaging.

The article looks at some research being done using ⁷⁴As tagged to bavituximab (an antibody). So being curious, I looked up the decay scheme for ⁷⁴As. It produces a β⁺ 66% of the time and a β^– 34% of the time with mean beta energies of 440 and 400 keV respectively. That means it should have good spatial resolution characteristics (travels a shorter distance from the decay point before annihilating). The half life of 17.77 days makes it less than ideal as an imaging agent though, but perfect for research because it allows researchers to follow the imaging characteristics of anything tagged to ⁷⁴As without having to do repeated injections.

From the article:

A study published in the latest issue of the journal Clinical Cancer Research (14 1377) shows that arsenic behaves as a promising functional imaging agent when linked to a developmental anti-cancer drug called bavituximab, an antibody that homes in on the blood vessels that feed cancerous tumours. The findings, which are based on animal studies, mark the first time that arsenic has been used to label antibodies for the detection of tumours.

Significantly, there appears to be little or no detectable uptake of bavituximab by normal organs, with 22 times as much bavituximab localized to the tumour compared to the liver when measured 72 hours post-injection. The study further showed no specific localization of bavituximab to blood or other tissues, including the heart, kidney, intestine, muscle, bone and brain.

It’s all still in the research phase but it sounds interesting. It will probably be a few years before anything is ready for clinical research on people but it sounds like there’s a lot of potential.

Abstract from the paper:

Purpose: We recently reported that anionic phospholipids, principally phosphatidylserine, become exposed on the external surface of vascular endothelial cells in tumors, probably in response to oxidative stresses present in the tumor microenvironment. In the present study, we tested the hypothesis that a chimeric monoclonal antibody that binds phosphatidylserine could be labeled with radioactive arsenic isotopes and used for molecular imaging of solid tumors in rats.

Experimental Design: Bavituximab was labeled with ⁷⁴As (β+, T1/2 17.8 days) or ⁷⁷As (β-, T1/2 1.6 days) using a novel procedure. The radionuclides of arsenic were selected because their long half-lives are consistent with the long biological half lives of antibodies in vivo and because their chemistry permits stable attachment to antibodies. The radiolabeled antibodies were tested for the ability to image subcutaneous Dunning prostate R3227-AT1 tumors in rats.

Results: Clear images of the tumors were obtained using planar {gamma}-scintigraphy and positron emission tomography. Biodistribution studies confirmed the specific localization of bavituximab to the tumors. The tumor-to-liver ratio 72 h after injection was 22 for bavituximab compared with 1.5 for an isotype-matched control chimeric antibody of irrelevant specificity. Immunohistochemical studies showed that the bavituximab was labeling the tumor vascular endothelium.

Conclusions: These results show that radioarsenic-labeled bavituximab has potential as a new tool for imaging the vasculature of solid tumors.