New technique images tumor vessel leakiness to predict breast cancer chemotherapy outcome

February 02, 2009

Chemotherapy is an integral part of modern cancer treatment, but it's not always effective. Successful chemotherapy depends on the ability of anticancer drugs to escape from the bloodstream through the leaky blood vessels that often surround tumors.

Predicting chemotherapy's efficacy could save thousands of individuals from unnecessary toxicity and the often difficult side effects of the treatments.

In a study published in the February issue of the journal Radiology, researchers describe a technique for determining the "leakiness" of tumor blood vessels using a simple digital mammography unit. The researchers designed nanometer-sized capsules containing a contrast agent that could only leak into tumors with blood vessels that were growing and therefore leaky. The digital mammography-based quantification of "leakiness" is closely correlated to the ability of a clinically approved chemotherapy agent to enter the tumor, allowing the researchers to predict the agent's therapeutic efficacy.

"We developed a quantitative way to measure the leakiness of the blood vessels, which is directly linked to the amount of drug that gets to the cancer and in turn determines effectiveness," said Ravi Bellamkonda, a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. "By simply measuring how much contrast agent reaches the tumor, we can predict how much of a clinically approved chemotherapeutic will reach the tumor, allowing physicians to personalize the dose and predict effectiveness."

In some cases, one chemotherapy drug may not be effective in treating the tumor, but this new technique allows oncologists to investigate other drugs sooner since they know the drug is reaching the tumor. Studies are currently underway to determine if mammography can predict the optimal dose of a wide range of breast cancer chemotherapeutics.

Bellamkonda and Coulter Department postdoctoral fellow Efstathios Karathanasis collaborated on this study with Ioannis Sechopoulos, an assistant professor in radiology at Emory University; Andrew Karellas, a former professor in the Emory University Winship Cancer Institute currently at the University of Massachusetts Medical School; and Ananth Annapragada, an associate professor of health information sciences at the University of Texas, Houston. The project was funded by the National Science Foundation and Georgia Cancer Coalition.

For the study, a long-circulating nanometer-scale liposomal capsule filled with iodinated contrast agent was injected into rats with six-day-old breast cancer tumors. For the next three days, the researchers collected digital mammography images of the animals and compared the pre- and post-injection grayscale intensity values to study the dynamics of how the contrast agent accumulated in the tumor over time.

"During the three-day time course, some tumors exhibited a rapid and significant increase in image brightness, meaning the contrast agent was accumulating in the tumor, whereas other tumors showed a slow and low increase," said Bellamkonda, who is also a Georgia Cancer Coalition Distinguished Scholar.

While the brightness of the tumors in the images changed significantly, no variations were observed in non-tumor areas or in the tumors of animals that did not receive the contrast agent. Immediately after the imaging was completed and the leakiness of each individual cancer vessel was quantified, the animals were intravenously injected with a clinically approved chemotherapy drug, liposomal doxorubicin.

Results showed that the chemotherapeutic drug slowed the progress of the tumor. The variability in uptake of the contrast agent by the tumors, as measured during the three-day imaging sessions, provided an accurate prognosis of the effect of liposomal doxorubicin on tumor growth rate.

"When we plotted the post-treatment tumor growth rate versus the intensity of leakiness, there was a significant and strong correlation," noted Bellamkonda. "The tumors in which the nanocarrier leaked out and accumulated the most in the tumors during the initial three-day test were the ones that responded best to the treatment."

To verify that the intensity changes in the images were caused by the nanocarrier and not endogenous changes in the tumor tissue, liposomal probes tagged with a fluorescent dye were injected into the animals. By looking at histological tumor sections, the researchers showed that the location of the increased image brightness and the fluorescent dye were the same.

"This study showed that higher uptake of the probe by the tumor related to leakier vasculature and suggested a better therapeutic outcome of liposomal doxorubicin," said Bellamkonda. "Imaging the integrity of the tumor vasculature like this may allow cancer treatment to be more patient-specific and potentially spare patients from chemotherapy if it is not going to be effective."

While the goal of the study reported in the journal was not to induce tumor regression, the researchers plan to investigate whether the liposomal probes can be used for this purpose in the future. To further develop and commercialize these multifunctional probes, Bellamkonda and Annapragada founded a start-up company called Marval Biosciences, Inc.

The researchers also want to investigate whether the leakiness of tumor vasculature represents a parameter that is useful for clinical diagnosis or tumor characterization.

"We want to study the molecular basis for blood vessel leakiness," said Bellamkonda. "We want to understand why there is variation in leakiness and chemotherapy effectiveness among individuals with tumors of the same type, size and stage."

Georgia Institute of Technology Research News

---

---

	The Chemotherapy Survival Guide: Everything You Need to Know to Get Through Treatment by Judith McKay (Author), Tammy Schacher RN OCN MSN (Author) When you're facing cancer treatment, it's easy to feel overwhelmed and alone. Between the hospital or clinic environment and the medical terminology used by doctors and health care professionals, you may feel as though you've entered a foreign country.Written by two experienced oncology nurses, this compassionate and comprehensive guide explains in plain English everything you need to know about your treatment, including what you can expect at each stage of chemotherapy and what you can do to prevent or minimize side effects. Packed with practical suggestions, nutritional advice, relaxation skills, and other techniques to help strengthen your body and calm your mind, The Chemotherapy Survival Guide is a must-have resource for anyone navigating this difficult...
	Handbook of Cancer Chemotherapy (Lippincott Williams & Wilkins Handbook Series) by Roland T. Skeel (Author), Samir Khleif (Author) Skeel's Handbook of Cancer Chemotherapy combines in one place the most current rationale and specific details necessary to safely administer chemotherapy for most adult cancers. The handbook is a practical, diseased-focused pocket reference that emphasizes the best current medical practice as it relates to the delivery of chemotherapeutic drugs. By focusing on specific plans for treatment, the book is an invaluable resource for the daily care of cancer patients.
	Chemotherapy and Radiation For Dummies by Alan P. Lyss (Author), Humberto Fagundes (Author), Patricia Corrigan (Author) An informative, compassionate guide for cancer patients and their loved onesEach year, more than 1 million people get treated for cancer, and most of these will undergo chemotherapy, radiation therapy, or both. This reassuring, optimistic guide helps people get a handle on treatment options and explains in plain English how chemotherapy and radiation therapy really work. It offers detailed advice on how to alleviate and cope with side effects-which range from hair loss to nausea to anemia-and describes how good nutrition, meditation, support groups, and other techniques and resources can help in the recovery process.
	83 Ways of Mitigating Chemotherapy Side Effects It was May 2002, when my father complained of an uneasiness in his stomach, he was experiencing slight pain in generally the lower abdomen. My father was a healthy person otherwise, with no major complaints apart from aches in the leg which we normally attributed to his walking long distances, as that was his hobby and he was very environment conscious in the times when people were not talking about environment or it had not become a fad to talk about. We gave him the usual home therapy for uneasiness, but the complaint persisted hence we took him to our family physician who was also like a family member. She immediately suspected something fishy and asked us to get a sonography done. The result was shocking for our family. My father was suffering from a unique syndrome atleast...
	Nurse's Chemotherapy Quick Pocket Reference by Debra S. Prescher-Hughes (Author) Nurse's Chemotherapy Quick Pocket Reference is a portable, quick-reference guide that provides quick access to the essentials of chemotherapy dosing administration and is arranged alphabetically by cancer type. This resource covers drug information for over 40 cancer types including bladder cancer, breast cancer, colorectal cancer, gastric cancer, head and neck cancer, leukemia, lung cancer, ovarian cancer, prostate cancer, thyroid cancer, and more, and includes pre-treatment information, chair time, and major side effects for each drug entry. All the chemotherapy drug information you need in the palm of your hand!
	Questioning Chemotherapy: A Critique of the Use of Toxic Drugs in the Treatment of Cancer by Ralph W. Moss (Author) A revealing critique of chemotherapy, this book looks objectively at chemo's successes and failures.
	Chemo: Secrets to Thriving: From someone who's been there. by Roxanne Brown (Author), Barbara Mastej (Contributor), John S. Link M.D. (Contributor) The thought of chemotherapy can be overwhelming, but getting through it doesn’t have to be. Chemo: Secrets to Thriving helps lighten the load. In chronological order, step-by- step, you learn what might occur, why it happens, what you can do (with your doc’s approval), and who to contact for help. Chemo: Secrets to Thriving will be your friend, companion, and guide, giving you the resources to handle possible side effects and better manage your life during chemotherapy. Once you know the secrets in this book you may find yourself still able to enjoy life—and even thrive—while going through chemotherapy. Our endorsements aren’t from the usual celebrities, but from our celebrities: medical teams, fellow chemo travelers, and the people and places that support them.
	Cancer Chemotherapy and Biotherapy: Principles and Practice (Chabner, Cancer Chemotherapy and Biotherapy) by Bruce A. Chabner (Editor), Dan L. Longo (Editor) Updated to include the newest drugs and those currently in development, Cancer Chemotherapy and Biotherapy, Fifth Edition is a comprehensive reference on the preclinical and clinical pharmacology of anticancer agents. Organized by drug class, the book provides the latest information on all drugs and biological agents—their mechanisms of action, interactions with other agents, toxicities, side effects, and mechanisms of resistance. Chapters emphasize pharmacology and mechanisms of action at the molecular and cellular levels, followed by clinical activity and toxicity, both acute and delayed. The authors explain the rationale for use of drugs in specific schedules and combinations and offer guidelines for dose adjustment in particular situations. This edition's introduction includes...
	The Cancer-Fighting Kitchen: Nourishing, Big-Flavor Recipes for Cancer Treatment and Recovery by Rebecca Katz (Author), Mat Edelson (Author) A Culinary Pharmacy in Your Pantry The Cancer-Fighting Kitchen features 150 science-based, nutrient-rich recipes that are easy to prepare and designed to give patients a much-needed boost by stimulating appetite and addressing treatment side effects including fatigue, nausea, dehydration, mouth and throat soreness, tastebud changes, and weight loss. A step-by-step guide helps patients nutritionally prepare for all phases of treatment, and a full nutritional analysis accompanies each recipe. This remarkable resource teaches patients and caregivers how to use readily available powerhouse ingredients to build a symptom- and cancer-fighting culinary toolkit. Blending fantastic taste and meticulous science, these recipes for soups, vegetable dishes, proteins, and sweet and savory snacks...
	Physicians' Cancer Chemotherapy Drug Manual 2012 (Jones & Bartlett Learning Oncology) by Edward Chu (Author), Vincent T. DeVita Jr. (Author) Completely Revised And Updated For 2012, The Physicians’ Cancer Chemotherapy Drug Manual Is An Up-To-Date Guide To The Latest Information On Standard Therapy And Recent Advances In The Field. Written By World-Class Experts In Clinical Cancer Therapeutics, This Essential Reference Provides A Complete, Easy-To-Use Catalog Of Over 100 Drugs And Commonly Used Drug Regimens—Both On- And Off-Label—For The Treatment Of All The Major Cancers. Special Features: Revised To Reflect Rapid Advances In The Field, Incorporating Treatment Strategies And New Drugs Like Abiraterone Acetate, Eributin, Ipilimumab, Romidepsin, Sipuleucel-T, And Vandetanib. A Specific Chapter Focused On Profiling Antiemetic Drug And Antiemetic Treatment Regimens. Diagrams Of Drug Structures And Pathways For Many Of The...