03:13am Monday 16 December 2019

New Tumor-Targeting Agent Images and Treats Variety of Cancers

What’s more, years of animal studies and early human clinical trials show that this tumor-targeting alkylphosphocholine (APC) molecule can deliver two types of “payloads” directly to cancer cells: a radioactive or fluorescent imaging label, or a radioactive medicine that binds and kills cancer cells.

This series of images shows how the alkylphosphocholine (APC) molecule targets and illuminates cancer cells.

The results are featured in today’s issue of the journal Science Translational Medicine with the journal’s cover illustration and a podcast.

Exploiting a Tumor’s Weakness

The APC targeting molecule was created to exploit a weakness shared by tumors as diverse as breast, brain, colorectal, lung, prostate and skin cancers. Unlike normal cells, cancer cells lack the enzymes to metabolize APC and similar phospholipid ethers that merge with cell membranes.

When given intravenously, APC goes throughout the body – even across the blood-brain barrier – and inserts into the surfaces of cancer cells. Then the APC – and any linked imaging or treatment medications – are incorporated into cancer cells for days to weeks, resulting in direct cancer cell imaging or treatment.

The APC analogs were able to tag 55 of 57 different cancers. This large study had multiple stages, including testing first in cancer cell lines, transgenic animal cancer models, rodents implanted with human cancers, and finally in human patients with different cancers such as breast, lung, colorectal and glioblastoma (brain cancer).

“I started as a skeptic; it’s almost too good to be true,’’ says co-lead author Dr. John S. Kuo, associate professor of neurosurgery and director of the comprehensive brain tumor program at the UW School of Medicine and Public Health. “It is a very broad cancer-targeting agent – both because of the many different cancers that tested positive, and its ability to detect cancer throughout the body. The APC analogs revealed clusters of cancer in patients that were small, asymptomatic and previously undetected by physicians.”

Potentially Superior Imaging Method

A virtual colonoscopy movie shows how APC distinguishes between benign and cancerous polyps.

Kuo specializes in surgery and treatment for brain tumors, and also leads the UW Carbone Cancer Center CNS Tumors group that runs many national cancer clinical trials.

Many scientists and doctors now think one reason cancer is difficult to cure is because current treatments fail to eradicate cancer stem cells that can seed and regrow tumors. He says it is encouraging that the APC analogs also picked up cancer stem cells and could also likely target them for further treatment.

“APC is a potentially superior imaging method because on standard clinical imaging, surgical scars, post-treatment effects, inflammation, or infection can look very similar to recurrent tumor; it is difficult to be certain if cancer has truly returned,’’ he says.

APC imaging can potentially prevent interpreting a “false positive” result of standard imaging as cancer recurrence and treatment failure, so cancer patients can continue effective therapies and avoid the risks and costs of “second look” surgeries.

In addition, Kuo says the fluorescent intraoperative APC imaging might help make cancer surgeries more effective and safer; any cancer cells that cannot be safely removed can be targeted afterward with radioactive APC therapy.

Dr. Jamey P. Weichert, associate professor of radiology, is also co-lead author of this large multidisciplinary study. He cofounded and serves as chief scientific officer of Cellectar Biosciences, Inc., a Madison-based company developing the APC molecules for cancer imaging and therapy.

Jamey Weichert (from left), Lance Hall and John Kuo collaborated on the study.Jamey Weichert (from left), Lance Hall and John Kuo collaborated on the study.

Other UW faculty who contributed to the study include lung cancer expert Dr. Anne Traynor, associate professor of medicine; cancer imaging experts Dr. Lance Hall, assistant professor of radiology, and Dr. Perry Pickhardt, professor of radiology. Pickhardt is a pioneer of “virtual colonoscopy.” 

A virtual colonoscopy movie in this study shows how APC distinguishes between benign and cancerous polyps during a virtual colonoscopy performed on a rat colorectal cancer model developed by Dr. William Dove at UW’s McArdle Laboratory for Cancer Research

Other UW and Cellectar co-authors are Dr. Paul A. Clark, Dr. Irawati K. Kandela, Dr. Abram M. Vaccaro, Dr. William Clarke, Dr. Marc A. Longino, Dr. Anatoly N. Pinchuk, Mohammed Farhoud, Dr. Kyle I. Swanson, Dr. John M. Floberg, Dr. Joseph Grudzinski, Dr. Benjamin Titz, Hong-En Chen, and Dr. Chris Pazoles.

University of Wisconsin School of Medicine and Public Health

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