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Cancer-Specific Information

Cancer imaging involves the use of molecular imaging technology to accurately diagnose, manage and treat many types of cancer.

Cancer imaging, or tumor imaging, allows physicians to:

Identify Tumor Properties and Growth

Tumor imaging allows physicians to accurately characterize a tumor's biological properties and to select the treatment most likely to be effective based on the tumor's characteristics.
Monitor Treatment

Molecular imaging can provide much quicker information about treatment effectiveness. For example, a PET Scan allows physicians to see within days of treatment how the tumor was affected by the therapy. CT scans can only show if cancer cells are still active by waiting for an increase in size, which shows up months later.
Treat the Tumor

Through radioimmunotherapy, physicians can deliver concentrated, cell-killing doses of radiation directly to the tumor, decreasing radiation exposure to healthy tissue.

Click on the image to view the report on the "Clinical Utility of PET in a Variety of Tumor Types" from the Journal of the National Comprehensive Cancer Network.

Clinical Applications of MI

Molecular imaging (MI) has made a significant impact on the field of oncology and is playing an increasingly important role in the diagnosis and treatment of cancer, through clinical applications, research and drug development. MI has become part of standard care for many types of cancer. MI allows physicians to accurately characterize tumor or biological processes, extent, location, response to treatment and prognosis. Molecular imaging is also increasingly being used for therapy, providing a means of target-specific drug delivery.

Diagnosis, staging and re-staging

Molecular imaging helps determine the location, extent and metabolic activity of the disease.

PET, often used in conjunction with computed tomography (CT), is used to diagnose and determine the stage of many types of cancer, including lung, head and neck, colorectal, esophageal, lymphoma, melanoma, breast, thyroid, cervical, pancreatic and brain cancers. It is also used to stage and re-stage common cancers such as lymphoma, lung, breast, prostate and colorectal cancers.
PET/CT is a useful tool for managing cancer that has metastasized.

Treatment planning

Molecular imaging provides information for better decision-making with regard to chemotherapy (continue, abandon or change) surgery (biopsy, attempt surgical resection, abort planned resection) and radiotherapy (defining radiation therapy port boundaries, palliation or attempted cure).

FDG-PET/CT is becoming an integral part of the initial work-up in patients scheduled to undergo radiation therapy.

Predicting Outcome & Monitoring Treatment Response

PET scans provide an early and accurate way to determine if cancer is responding to treatment. In addition to enabling changes in patient management to be made in real time, it also helps predict treatment response before therapy is initiated.

Therapy

Molecular radiotherapy (MRT) is a systemically administered, targeted therapy that delivers radiation at the cellular and molecular level. In contrast to chemotherapy, wherein all proliferating cells are affected, MRT delivers radiation to only those cells that express cancer markers.

The prototypical example of molecular radiotherapy is radioiodine treatment of thyroid cancer. MRT is also used to treat indolent non-Hodgkin’s lymphoma, using Zevalin^®, an FDA-approved, antibody-based molecular radiotherapeutic.

Radiolabeled peptides have shown to be beneficial in the treatment of neuroendocrine tumors. Unlike the therapeutic regimen of Zevalin, which is based on intact antibodies, peptides are typically made up of fewer than 50 amino acids. ¹¹¹In-DTPA-octreotide (Octreoscan), was approved by the FDA in 1994 for imaging/detection of neuroendocrine tumors with somatostatin receptors based on trials conducted exclusively outside the of the United States.

Both promising new antibody-based and peptide-based MRTs continue to be developed and comparative trials will be needed to determine how these will be used with current treatment against neuroendocrine tumors.

Metaiodobenzylguanidine (MIBG) is an aralkylguanidine analog of catecholamine precursors, structurally similar to norepinephrine that concentrates within secretory granules of catecholamine producing cells. It has been labeled with ¹²³I for diagnostic imaging and with ¹³¹I for therapy of neuroblastoma, pheochromocytoma, and, to a lesser extent, other neuroendocrine tumors.

Imaging and Therapeutic Technologies Used in Oncology

Molecular imaging technologies used in oncology include:

PET-CT (Positron emission tomography and computed tomography
SPECT-CT (Single-photon emission computed tomography and CT)
Magnetic Resonance (MR) spectroscopy
Lymphoscintigraphy (for melanoma, breast cancer and GYN cancers)
PMSA study
Radioimmunotherapy (RIT)
Molecular radiotherapy (MRT)

Advantages

PET/CT provides information — non-invasively — that once would have required many medical studies. The information provided often eliminates the need for exploratory surgery and other invasive medical procedures
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 can help individuals avoid unnecessary or unproductive surgery or treatment.
PET scans may eliminate the need for surgical biopsy by differentiating benign from malignant lesions
PET scans are currently the most effective means of detecting a recurrence of some cancers.
In contrast to chemotherapy, where all proliferating cells are affected, molecular radiotherapy (MRT) delivers concentrated doses of radiation directly to the tumor, decreasing radiation exposure to healthy tissue and potentially reducing side effects.

Limitations

False-Positive and False-Negative Results PET/CT

FDG is not only a cancer-specific imaging agent, false positive results may be observed with benign diseases. False positive results are commonly observed in areas of active inflammation or infection, with a reported false positive rate of approximately 13 percent and false negative rate of approximately 9 percent. Accumulation of FDG only indicates enhanced cellular metabolism, irrespective of the nature of the cells. Areas of activated macrophages as well as metabolically active carcinomas will all accumulate FDG. Due to the limited specificity of FDG-PET/CT in excluding malignancy, FDG positive lymph nodes and metabolically active masses require histologic assessment to avoid incorrect diagnosis and potentially limiting treatment options for patients. The absences of FDG accumulation in lesions and lymph nodes is highly predictive for the absence of active disease, but false negative results can also be observed in malignancies with low metabolic activities.¹

¹Carter K, et al “Common Causes of False Positive F18 FDG PET/CT Scans in Oncology” Brazilian Archives of Biology and Technology 2007; 50: 29-35, September 2007–.

Radiation Risk

Nuclear medicine uses very small amounts of radioactive materials to diagnose and treat disease. The radiation risk involved in these procedures is very low compared with the potential benefits.

Insurance Coverage

Medicare and Medicaid cover PET-CT studies for many but not all cancers. Major insurance companies and health maintenance organizations also provide coverage for PET-CT studies for cancer. Patients should check with their own insurance company for specific information on their health plan’s coverage and payment policies.

Patients being treated for a cancer that is not currently covered by insurance may be eligible for reimbursement by participating in the National Oncologic PET Registry (NOPR). Information collected in this database will help the Centers for Medicare and Medicaid Services (CMS) determine whether PET scans should be covered for other types of cancer, in addition to those that are currently reimbursable under Medicare.

Research

Molecular imaging plays an important role in research into the causes and treatments of cancer by helping to:

elucidate the basic mechanisms underlying cancer biology
identify the most promising strategies for human clinical trials by providing preclinical imaging to characterize a tumor and its response to therapy
develop new drugs
using molecular-targeted radionuclide imaging, more effective, less toxic drugs for lymphoma have been developed and approved.

On the Horizon

Personalized Cancer Treatment

Molecular imaging and therapy are on the forefront of the trend toward personalized cancer treatment. The goal is to be able to accurately assess variables (variations in pharmacokinetics in whole body, organs and tumors; varying receptor statuses and proliferative/apoptotic rates in tumors;) and to individualize treatments to optimize response and minimize toxicity.

Increasingly, MI is able to assist practitioners in:

characterizing a tumor’s biological properties and the selection of a therapeutic regimen based on those characteristics as well as the unique biologic characteristics of the patient
determining a patient’s response to specific drugs and accurately assessing the effectiveness of a treatment regimen, early in the course of treatment
adapting treatment plans quickly in response to changes in cellular activity.

Molecular Imaging Biomarker Use in Oncology

Molecular imaging will likely become established as a tool for measuring biomarkers, or indicators of disease or therapeutic effects. Trials using a variety of molecular imaging techniques to validate this function are underway.

Potential uses of molecular imaging biomarkers include:

surrogate endpoints—biomarker intended as a substitute for a clinical endpoint, such as tumor shrinkage.
prognostic biomarkers—used prior to treatment to predict negative and positive results, e.g., hypoxic status of tumor.
predictive biomarkers—used to assess the effect of drug treatment, e.g., FDG-PET in lymphoma.

The potential benefits of imaging biomarkers in clinical trials include:

determining if a patient’s tumor is likely to respond to specific treatments
assessing after one or two treatments if a tumor is dying, even if it is not shrinking in size
determining which patients are at high risk of tumor recurrence
evaluating whether an experimental therapy is effective for tumor treatment.

Antigen-Specific Therapy

As the fields of molecular biology and genomics advance, tumor properties and pathways will be revealed, leading to a set of new cancer specific targets. Molecular radiotherapies can be developed to target tumor cells based on these advances.

Targeting CD20 in non-Hodgkin’s lymphoma is an example of antigen-specific therapy.
Molecular radiotherapy has therapeutic potential for other types of cancers including bone metastases, prostate, metastatic melanoma, ovarian, leukemia, high-grade brain tumors, metastatic colorectal cancer and neoplastic meningitis.

Nanomedicine

Cancer cells have unique properties that can be exploited by nanoparticles. Guided by and/or in conjunction with molecular imaging technologies, nanoparticles can be targeted at cancer cells to:

detect and monitor disease
deliver drugs, such as chemotherapy and gene therapy
treat through ablation.

Other advancements include:

novel radiotracers to image critical cancer processes including cell death, tumor proliferation, angiogenesis, hypoxia. Fluorestradiol (FES) measures estrogen receptors to track tumors and has been tested in clinical trials. F-18 fluorothymidine (FLT) looks at cellular growth and proliferation and F-18 fluoromisonidazole (FMISO) is a marker of tumor hypoxia, being tested in clinical trials. These agents can also be used to select and evaluate targeted therapies, such as those designed to target hypoxia, angiogenesis, chemotherapeutic resistance and others.

Other probes are being developed to measure the early effects of cancer gene expression, including the differential or aberrant expression of:

glycolysis
cell surface receptor expression
DNA synthesis
cell membrane synthesis
hypoxia
angiogenesis
blood flow
cell migration
cytokine signaling.

reporter-probe pairs for molecular-genetic imaging. A reporter gene is a gene whose product can be readily detected and either fused to the gene of interest or replace by it. The main applications for these reporters include monitoring gene expression levels, investigating dynamic molecular interactions between proteins, studying cellular interactions, tracking cells in normal and abnormal development or in cell transplantation therapy and monitoring gene replacement therapy. Optical reporter genes are the most commonly used and widely developed for imaging. A new emerging class of reporter genes encodes for proteins with an affinity for radioisotopes or positron emitter probes.

development of agents that can be used concurrently as diagnostic and therapeutic agents, an emerging field called ‘theranostics.’

Technologies

Technologies under development include:

Optical imaging For imaging gene expression; cell trafficking; therapeutic monitoring; the detection of ovarian cancer, malignant skin lesions, lymphoma, and intestinal adenoma; drug delivery and photoablation. Optical imaging is primarily used as a research tool although some applications are entering initial clinical testing.
Targeted Ultrasound Providing differential diagnoses of cancer, including breast, ovarian, head and neck, prostate, liver and pancreatic as well as drug delivery
High-field MR spectroscopy As an adjunct to breast MRI, distinguishing malignant from benign tissue; helping to differentiate between recurrent brain tumors and changes due to radiation treatments; and guiding radiation treatment of recurrent brain tumors and prostate cancer
Diffusion Tensor Imaging (DTI) For diagnosing cerebral ischemia and investigating brain disorders including tumors. DTI measures the anisotropy of microscopic water molecules surrounding the brain’s white matter fibers.
Fusion imaging Provides the ability to view molecular information within an anatomic context. This capability can be applied to PET, US, SPECT, MRI, MR spectroscopy and a growing range of optical technologies.