Fact Sheet: Molecular Imaging and Colorectal Cancer

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Cancer that begins in the colon, the longest part of the large intestine, is called colon cancer. Cancer that begins in the rectum located at the end of the colon is called rectal cancer. Cancer that starts in either of these organs is often referred to as colorectal cancer.

According to estimates from the National Cancer Institute, more than 149,500 new cases of colon and rectum cancer were diagnosed in the United States and nearly 52,980 people died from the disease in 2021. In the United States, colorectal cancer is the third leading cause of cancer-related deaths in men and in women, and the second most common cause of cancer deaths when men and women are combined.

New developments in molecular imaging technologies are dramatically improving the ways in which colorectal cancer is diagnosed and treated. Research in molecular imaging is also contributing to our understanding of the disease and directing more effective care of patients with colorectal cancer.

What is molecular imaging?

Molecular imaging is a type of medical imaging that provides detailed pictures of what is happening inside the body at the molecular and cellular level. Where other diagnostic imaging procedures—such as x-rays, computed tomography (CT), and ultrasound—predominantly offer anatomical pictures, molecular imaging allows physicians to see how the body is functioning and to measure its chemical and biological processes.

Molecular imaging offers unique insights into the human body that enable physicians to personalize patient care. In terms of diagnosis, molecular imaging is able to:

• provide information that is unattainable with other imaging technologies or that would require more invasive procedures such as biopsy or surgery
• identify disease in its earliest stages and determine the exact location of a tumor, often before symptoms occur or abnormalities can be detected with other diagnostic tests

As a tool for evaluating and managing the care of patients, molecular imaging studies help physicians:

• determine the extent or severity of the disease, including whether it has spread elsewhere in the body
• select the most effective therapy based on the unique biologic characteristics of the patient and the molecular properties of a tumor or other disease
• determine a patient’s response to specific drugs
• accurately assess the effectiveness of a treatment regimen
• adapt treatment plans quickly in response to changes in cellular activity
• assess disease progression
• identify recurrence of disease and help manage ongoing care

Molecular imaging procedures are noninvasive, safe and painless.

How does molecular imaging work?

When disease occurs, the biochemical activity of cells begins to change. For example, cancer cells multiply at a much faster rate and are more active than normal cells. Brain cells affected by dementia consume less energy than normal brain cells. Heart cells deprived of adequate blood flow begin to die.

As disease progresses, this abnormal cellular activity begins to affect body tissue and structures, causing anatomical changes that may be seen on CT or MRI scans. For example, cancer cells may form a mass or tumor. With the loss of brain cells, overall brain volume may decrease or affected parts of the brain may appear different in density than the normal areas. Similarly, the heart muscle cells that are affected stop contracting and the overall heart function deteriorates.

Molecular imaging excels at detecting the cellular changes that occur early in the course of disease, often well before structural changes can be seen on CT and MR images.

Most molecular imaging procedures involve an imaging device and an imaging agent, or probe. A variety of imaging agents are used to visualize cellular activity, such as the chemical processes involved in metabolism, oxygen use or blood flow. In nuclear medicine, which is a branch of molecular imaging, the imaging agent is a radiotracer, a compound that includes a radioactive atom, or isotope. Other molecular imaging modalities, such as optical imaging and molecular ultrasound, use a variety of different agents. Magnetic resonance (MR) spectroscopy is able to measure chemical levels in the body, without the use of an imaging agent.

Once the imaging agent is introduced into the body, it accumulates in a target organ or attaches to specific cells. The imaging device detects the imaging agent and creates pictures that show how it is distributed in the body. This distribution pattern helps physicians discern how well organs and tissues are functioning.

What molecular imaging technologies are used for colorectal cancer?

Positron emission tomography (PET) scanning and PET combined with computed tomography (PET-CT) is used for colorectal cancer. 

What is PET?

PET involves the use of an imaging device (PET scanner) and a radiotracer that is injected into the patient’s bloodstream. A frequently used PET radiotracer is ¹⁸F-fluorodeoxyglucose (FDG), a compound derived from a simple sugar and a small amount of radioactive fluorine.

Once the FDG radiotracer accumulates in the body’s tissues and organs, its natural decay includes emission of tiny particles called positrons that react with electrons in the body. This reaction, known as annihilation, produces energy in the form of a pair of photons. The PET scanner, which is able to detect these photons, creates three-dimensional images that show how the FDG is distributed in the area of the body being studied.

Areas where a large amount of FDG accumulates, called ‘hot spots’ because they appear more intense than surrounding tissue, indicate that a high level of chemical activity or metabolism is occurring there. Areas of low metabolic activity appear less intense and are sometimes referred to as ‘cold spots.’ Using these images and the information they provide, physicians are able to evaluate how well organs and tissues are working and to detect abnormalities.

PET-CT is a combination of PET and computed tomography (CT) that produces highly detailed views of the body. The combination of two imaging techniques—called co-registration, fusion imaging or hybrid imaging—allows information from two different types of scans to be viewed in a single set of images. CT imaging uses advanced x-ray equipment and in some cases a contrast-enhancing material to produce three dimensional images.

A combined PET-CT study is able to provide detail on both the anatomy and function of organs and tissues. This is accomplished by superimposing the precise location of abnormal metabolic activity (from PET) against the detailed anatomic image (from CT).

PET/CT (A and B) of patient with colorectal cancer shows increased activity of tumor as indicated by the arrows.  (C) CT and (D) PET/CT scans depict bone and liver tumor growth. (E) CT and (F) PET/CT scans show the primary tumor.
Source: http://tech.snmjournals.org/content/38/1/6.full

How is PET used for colorectal cancer?

Physicians use PET-CT studies to:

• diagnose and stage: by determining the exact location of a tumor, the extent or stage of the disease and whether the cancer has spread in the body.
• plan treatment: by selecting the most effective therapy based on the unique molecular properties of the disease and of the patient’s genetic makeup
• evaluate the effectiveness of treatment: by determining the patient’s response to specific drugs and ongoing therapy. Based on changes in cellular activity observed on PET/CT images, treatment plans can be quickly altered.
• manage ongoing care: by detecting the recurrence of cancer

How is PET performed?

The procedure begins with an intravenous (IV) injection of a radiotracer, such as FDG, which usually takes between 30 and 60 minutes to distribute throughout the body. After the radiotracer is distributed, the patient is placed in the PET scanner where special detectors are used to create a three dimensional image of the FDG distribution.

Scans are reviewed and interpreted by a qualified imaging professional such as a nuclear medicine physician or radiologist who shares the results with the patient’s physician.

What are the advantages of PET for people with colorectal cancer?

• PET is a powerful tool for diagnosing and determining the stage of many types of cancer, including colorectal
• By detecting whether lesions are benign or malignant, PET scans are able to eliminate the need for surgical biopsy
• PET is more accurate than CT for staging colorectal cancer
• PET is able to confirm or rule out the presence of secondary cancers in the liver or lung, providing valuable information that directly affects treatment options
  • PET-CT is recommended for colorectal cancer patients whose cancer has spread to the liver and who opt for surgery to remove the diseased section of the liver. The five-year survival rate of patients who are screened with PET prior to undergoing the surgery is higher than for patients who are not imaged with PET prior to surgery.
• PET and PET-CT scans prompt changes in the treatment of more than one-third of patients registered in the National Oncologic PET Registry (NOPR)
• PET scans are currently the most effective means of detecting a cancer recurrence

• PET-CT is helpful for nearly all aspects of colorectal cancer diagnosis and treatment, including identifying incidental cancers in the colon

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  •  PET is able to distinguish between cancer recurrences and post-therapy scarring in the colon

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  • PET is useful in detecting cancer recurrence in patients who have an increased blood protein called carcinoembryonic antigen (CEA)

Is PET covered by insurance?

PET scans are covered by Medicare and private insurance companies. Check with your insurance company for specific information on your plan.

What is the future of molecular imaging and colorectal cancer?

There are many new and emerging molecular imaging technologies that can benefit colorectal patients, including:

• fusion or hybrid imaging, in which two imaging technologies are combined to produce one image
• the use of PET imaging biomarkers, to identify individuals at risk for or in the early states of disease.
• radioimmunotherapy.

What is radioimmunotherapy (RIT)?

Radioimmunotherapy(RIT) is a personalized cancer treatment that combines radiation therapy with the precise targeting ability of immunotherapy, a treatment that mimics cellular activity in the body’s immune system.

In a healthy immune system, certain white cells are able to recognize invading organisms such as bacteria and viruses. The white cell secretes a protein substance called an antibody that identifies a feature of the foreign cell called an antigen. The antibody coats the invading cell, which enables other white cells to destroy it.

In immunotherapy, scientists create monoclonal antibodies in a laboratory that are designed to recognize and bind to the antigen of a specific cancer cell. In RIT, the monoclonal antibody is paired with a radioactive material. When injected into the patient’s bloodstream, the antibody travels to and binds to the cancer cells, allowing a high dose of radiation to be delivered directly to the tumor.

Several new radioimmunotherapy agents are under development or in clinical trials.