Application of Medical Isotopes in Diagnosis and Treatment of Cervical Cancer (Schenter, Lombardo)

The Application of Medical Isotopes in the Diagnosis and Treatment of Cervical Cancer Allison E. Lombardo and Robert E. Schenter

August 7, 2007

Advanced Medical Isotope Corporation (AMIC)

The Application of Medical Isotopes in the Diagnosis and Treatment of Cervical Cancer Allison E. Lombardo and Robert E.Schenter

Abstract Cervical Cancer represents a leading cause of ………..

Table of Contents 1.0 Introduction 2.0 Diagnostics 2.1 Positron Emission Tomography 2.2 F18 3.0 Therapeutics 3.1 Brachytherapy 3.2 Cs-137 3.3 Cf-252, Ir-192 4.0 Conclusions 5.0 References 6.0 Appendices 6.1 SNM 2006 Abstracts 6.2 SNM 2007 Abstracts

1.0 Introduction Although it is the second most common type of cancer in women, cervical cancer has still managed to affect a staggering number of females all over the world. In the U.S. alone, it creates 9,710 new cases and attributes to 3,700 deaths on average each year (1). Lately, more attention has been directed to cervical cancer because of its direct connection with the Human Papilloma Virus.

HPV is the most common sexually-transmitted infection in the United States (1). There are several different types, many of which are a direct cause of cervical cancer. With the introduction of the HPV Vaccination, women can now be protected against two of these types, which are responsible for causing approximately 70 percent of cervical cancers (1). This vaccination has heightened awareness among women of how easily the virus can be contracted and spread. Alarmingly, about 6.2 Americans become infected with HPV each year and it is estimated that over half of all sexually active men and women will become infected with the disease at some point in their lives (1). These frightening statistics should encourage women to seek proper and regular screening. Pap Tests are the most effective way to discover abnormalities as long as they are preformed every two or three years (2). Once discovered, the latest developments in the field of nuclear medicine aid in the diagnosis and treatment of this disease.

2.0 Diagnostics Physical diagnostic examinations such as Cytoscopy and Protoscopy are usually only performed in women with large tumors (3). Aside from these cases, diagnosis for cervical cancer is most often administered using medical isotopes.

For diagnosis, radio imaging is frequently conducted through the use of PET scans. Glucose tagged with radioactive Fluorine-18 is used in this procedure. PET scans are used, “To examine the size and progression of a known tumor. The method exploits the way in which normal glucose is metabolized by the body.

When a patient is injected with radioactive glucose, the cells of the body try to use it as they would normal glucose. However, the fluorine prevents the radioactive glucose from being completely metabolized.

Instead the glucose is trapped inside the cells. The patient is then scanned and doctors can see where the radioactive substance has been stored by analyzing the pattern of energy it emits. Cancerous tissue, which uses more glucose than normal tissue, absorbs more radioactivity and appears brighter on the PET images.” (4)

According to radiation oncologist Perry W. Grigsby, M.D., radioactive glucose is a very useful indicator for cervical cancer because cervical tumors vary more in their glucose uptake than other types of cancer. Researchers at the Washington University School of Medicine in St. Louis also notes “Cervical cancers that take up a lot of blood sugar, or glucose, are more resistant to treatment than those that are less glucose-hungry.” Standard therapy techniques have been ineffective in tumors with high glucose metabolism. Research is still being done to determine how to treat these highly resistant tumors (5). PET imaging with Fluorine-18 has been essential in the effort to learn more about this disease.

3.0 Therapeutics Treatment of cervical cancer can typically be given in one of two ways: surgery or radiation therapy. The age of the patient and what stage the cancer is at will determine which method is used.

Surgery most often means a hysterectomy will be performed, which involves removing the uterus and sometimes other areas in

the pelvic region. The second option, radiation therapy, employs the use of medical isotopes in two different methods, External Beam Radiation and Intercavitary Radiation. First, External Beam Radiation is given which involves direct-radiation applied at the lymph nodes along the pelvic wall for five days a week for six weeks (6). Next, Intercavitary Radiation, also referred to as brachytherapy, follows. Brachytherapy procedures enlist a radioactive source, usually Cesium-137, which is housed in a long stainless steal tube called a tandem. The tandem is “inserted into the uterus” and “placed against the cervix as close to the cancerous cells as possible. Commonly, two or more radiation treatments are administered for about 35 hours each time.” Occasionally, a needle can be used to insert the radiation implants directly into the tumor (6). Both External Beam Radiation and brachytherapy are used because each procedure targets a different portion of the cancer.

According to Evansville Cancer Center, “External Beam irradiation delivers a homogenous dose to the primary tumor and potential sites of regional spread while brachytherapy optimizes high doses to the bulk of the disease (cervix and paracervical tissue) and limits does to sensitive GI structures” (7). Radiation techniques would not be as successful without both procedures.

Cesium-137 is currently the most common isotope being used in brachytherapy procedures. In fact, the use of this isotope has even spread to India. In India, an alarming number of cervical cancer cases exist partially due to “inadequate and costly facilities” and lack of knowledge about the disease: (Insert 8) The latest developments to the brachytherapy procedure, however, involve using other isotopes instead of Cesium-137.

Californium-252 has been used in several studies and is being evaluated more thoroughly: (Insert articles) Brachytherapy with Californium-252 (9, 10) Brachytherapy with Californium-252 vs. with Cesium-137 (11)

Stage IIIB Treatment with Californium-252 Brachytherapy (12) Gamma Brachytherapy vs. Neutron Brachytherapy with Cf-252 (13) There has also been mention of use of Iridium-192 in the standard brachytherapy procedures, “Intracavitary gynecologic cancers, usually within the cervix, are treated using a temporary implant.

Cesium-137 or Iridium-192 sources are inserted in to the treatment site…” (14). There have also been other developments that incorporate Iridium-192 into an entirely new High Dose Rate (HDR) Brachytherapy Unit: (Insert 15) It is because of high success rates of radiation therapy that has allowed many patients to continue living normal lives after treatment. Several medical isotopes have become key ingredients in the fight against cervical cancer. Hopefully in the near future more medical isotopes can be added to this list.

4.0 Conclusions 5.0 References 1-FDA News 2-PDF-Pap Tests 3-ACS-Diagnosis 4-Radioactive Glucose-saved 5-Dangerous Glucose 6-About.com 7-Evansville 8-India PDF 9-A Review 10-Five year cure 11-Efficacy

12-Wiley 13- Isotron/Springerlink 14-Brachytherapy 15-Integrated

6.0 Appendices 6.1 SNM 2006 Abstracts 6.2 SNM 2007 Abstracts