Radioimmunoscintigraphy using Prostascint (Capromab Pendetide) Essay Example for Free

Radioimmunoscintigraphy using Prostascint (Capromab Pendetide) Essay Abstract   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Prostate cancer is one of the most common malignancies encountered among the men over the age of 65 years in the U.S. Proper treatment of patients with prostate cancer requires the determination of exact extent of cancer spread. Conventional imaging modalities like CT and MRI have proved to be of little use. Newer imaging modality involving radioimmunoscintigraphy using Prostascint has emerged as a useful diagnostic test for management of cases of carcinoma of prostate, particularly patients with localized disease and those showing evidence of recurrence following radiotherapy. Prostascint imaging serves as a reliable, noninvasive means of differentiating patients with organ-confined disease from those with metastatic spread to lymph. Following a positive Prostascint scan confirmatory studies (biopsy of involved sites) must be undertaken prior to initiation of a definitive surgical procedure. In the modern era, high quality fused images, using CT or MRI with Prostascint scans, obtained from using higher-resolution gamma cameras, have further increased the value of radioimmunoscintigraphy. However well designed randomized controlled trials in future are required to prove the exact clinical role of Prostascint imaging in cases of prostate cancer. Table of contents Introduction†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦.4 Analysis of Prostascint Imaging†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦.5 Applications of Prostascint imaging†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦6 Newly diagnosed patients with biopsy-proven prostate cancer.6 Patients with rising levels of PSA following prostatectomy†¦..7 Challenges associated with the use of Prostascint imaging†¦.†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦.10 Safety and precautions†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦.11 Conclusion†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦13 References/ bibliography†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦l5 Radioimmunoscintigraphy using Prostascint (Capromab Pendetide) Introduction Prostate cancer is one of the most common malignancies encountered among the men over the age of 65 years in the U.S. During the year 2004, in the U.S 230,110 men were registered with the diagnosis of carcinoma prostate, whereas 29,900 died from it. (Jemal et al, 2004). Following the diagnosis of prostate cancer, one of the most important challenges for the clinician is to estimate the exact extent of the cancer (cancer staging) in order to undertake a proper treatment plan, which would be able to cure the cancer in its entirety in early as well as late cases. Information needed to stage prostate cancer depends upon tumor size, location, extra-prostatic extension, lymphatic involvement and distant metastases (Neal Kelly, 2004). In more than one third of cases of prostate cancer, by the time cancer is diagnosed, it has frequently involved the lymph nodes outside the pelvis, the most common ones being the periaortic lymph nodes (Neal Kelly, 2004). Treatment options and prognosis of localized cancer of prostate is different from the cases where the cancer has spread into the lymph nodes, contradicting the use of both surgery and radiotherapy, which works well for the localized disease. Hormone therapy and recently taxane based chemotherapy is used for the treatment of advanced disease (Neal Kelly, 2004). Presently the prediction of lymph node metastasis is not very accurate because, in the vast majority of cases, tissue examination for evaluating spread of cancer is based on biopsies involving a limited sample of the area with possible lymphatic spread. Conventional imaging modalities like computed tomography (CT) and magnetic resonance imaging (MRI) for detecting soft tissue metastasis, suffer from many disadvantages, which limits their use for this purpose (Neal Kelly, 2004). Lymphography as a diagnostic modality for visualization of lymphatic vessels and lymph nodes, following injection of radio opaque material in a lymphatic vessel has also proven to be inaccurate (Wolfgang, 2003). Significant advancements in the field of medical imaging have enabled the accurate estimation of cancer spread to a large extent. One such imaging technology is radioimmunoscintigraphy with Prostascint, which would be discussed in this paper. Analysis of Prostascint Imaging Radioimmunoscintigraphy is a nuclear medicine imaging technique which detectsn  signal from a radio labeled antibody that recognizes prostate tissue (Wolfgang, 2003). The most commonly studied monoclonal murine antibody for this purpose is (7E11-C53), capromab pendetide conjugated with the linker-chelator glycyl-tyrosyl-(N, ÃŽ-diethylenetriamine-pentaacetic acid)-lysine commonly known as Prostascint. In the most commonly used type of radioimmunoscintigraphy, Prostascint which has been radio labeled with indium-111(In-111) is given, followed by nuclear medicine imaging or SPECT imaging (Keane, Rosner, Wingo, McLeod, 2006). The most studied target for prostate cancer is the prostate-specific membrane antigen (PSMA), a glycoprotein expressed by prostate tissue, which is produced both by benign and malignant prostate epithelial cells. However it is expressed more abundantly in patients with prostate cancer, hormone-refractive disease, and prostate cancer metastases (Keane et al, 2006). Thus immunoscintigraphy is dependent on the degree of PSMA expression rather than the actual size of a metastatic lesion or the increase in the levels of PSA (prostate specific antigen). Applications of Prostascint imaging Prostascint (Capromab Pende ­tide) is commonly used as a diagnostic imaging agent, which shows significantly improved sensitivity for extra-prostatic cancer detection compared with conventional imaging modalities (Keane et al, 2006). According to the literature review by Keane et al, (2006), Prostascint, received Food and Drug Administration (FDA) approval in 1996 for its use as an imaging agent for the following purposes: (1) For the staging of patients, who have been recently diagnosed with histologically proven localized prostate cancer and are at a high risk for soft tissue metastases or (2) For the restaging of post prostatectomy patients with a rising PSA level. These applications of Prostascint have been described below in details: Newly diagnosed patients with biopsy-proven prostate cancer Prostascint imaging should be considered after a definitive diagnosis of localized prostate cancer, as proven by standard diagnostic investigations including chest x-ray, bone scan, CT scan, or MRI, which have been made prior to the initiation of definitive therapy in form of surgery or radiotherapy. Prostascint is not indicated in patients who are not at high risk for developing metastatic disease (Hinke et al, 1998). In fact it is especially administered to those patients who are at a high risk for pelvic lymph node metastasis as shown by an intermediate to high Gleason grade (a system for grading prostate cancer depending on the degree of differentiation of the malignant cells under a microscope) or by other diagnostic investigations carried out to evaluate the disease spread. In a study by Hinke et al (1998), scan positive extraprostatic regions, especially lymph nodes, following initial treatment, were histologically evaluated. The sensitivity and specificity of Prostascint imaging in   detection of extraprostatic disease was found to be 75% and   86% respectively, whereas the accuracy was found to be 81% and the positive predictive of Prostascint imaging in   detection of extraprostatic disease was found to be 79%. Thus, the study by Hinke et al (1998) shows that In-111 capromab pendetide (Prostascint) imaging has emerged as a promising diagnostic tool for detecting prostate cancer by having a significant impact on patient management through its detection of occult extra-prostatic disease in more than 50% of prostate carcinoma patients studied, and information regarding the presence of lymph node metastasis. It also shows that Prostascint imaging serves as a reliable, noninvasive means of differentiating patients with organ-confined disease from those with metastatic spread to lymph nodes and complements other modalities including prostate specific antigen (PSA), Gleason score, and clinical staging. Since Prostascint imaging can help predict the future involvement of lymph nodes in patients at high risk for extraprostatic disease it can therefore help in the selection of patients who may not benefit from definitive local therapy in form of surgery or radiotherapy. Patients with rising levels of PSA following prostatectomy Despite the ability of radical prostatectomy to eradicate prostate carcinoma, biochemical evidence of recurrent prostate carcinoma, in form of elevation in the serum PSA levels above the limit of detection may be seen in approximately 40% of patients, 15 years after they undergo surgery. The PSA test may become positive many years prior to a change in the bone scan or before the emergence of clinical evidence of recurrence (Neal Kelly, 2004). In more than 33% of cases the disease may recur locally in the prostatic fossa or regional lymph nodes or at distant sites. The presence of cancer recurrence requires further treatment in form of local salvage treatments or systemic therapy (Neal Kelly, 2004). Salvage therapy in form of external beam radiation may provide a therapeutic benefit only to those patients who have a localized recurrence. On the other hand, systemic therapy like hormonal therapy is usually recommended for patients with disseminated disease (lymphatic or metastatic spread) (Neal Kelly, 2004). Traditionally, most patients who show elevated serum levels of PSA post-surgically undergo a computed tomography (CT) scan of abdomen and pelvis or bone scintigraphy. The detection of tumor deposits on CT scans is size dependent i.e. the size of the tumor deposits should be more than 10–15 mm prior to detection. Further more, CT scan is not able to differentiate whether the lymph node is enlarged due to the presence of inflammation or metastasis (Neal Kelly, 2004). Thus the finding of radiographically enlarged lymph nodes is not diagnostic of carcinoma. Recurrence of prostate cancer after radiotherapy presents several challenges for the clinician regarding appropriate management. It is of utmost importance to identify correctly those patients with persistent localized disease and the potential to benefit from curative therapy (Keane et al, 2003). The localization of the extent of recurrent disease after radical prostatectomy is especially important for patients showing rising levels of PSA after prostatectomy and are being considered for salvage radiation therapy. However this is difficult with presently available techniques and may greatly influence subsequent clinical management (Raj, Partin, Polasiik, 2002). Prostascint imaging would greatly help in providing solution to this problem. Patients showing a positive result with radioimmunoscintigraphy, demonstrating that the cases with disease spread outside the pelvis can be spared inappropriate treatment, with radiotherapy, thus helps in reducing the associated morbidity and expense (Keane et al, 2006). Raj et al (2002) conducted a study to determine the use of indium- 111 labelled Prostascint imaging to detect recurrent prostate carcinoma radiographically in men with early biochemical evidence of failure (serum PSA levels less than or equal to 4.0 ng/mL) and tried to assess the minimum rise in serum PSA level, which would be necessary for imaging recurrent disease. Preoperatively, all patients had negative bone scans and negative lymph nodes on histopathological biopsy, and they did not undergo   any therapy including   hormonal ablation, chemotherapy, or radiation therapy preoperatively or postoperatively until the (111)In labeled Prostascint imaging was performed. The results of this study demonstrated that the Prostascint imaging is capable of detecting recurrent disease irrespective of level of serum PSA increase. Postive results on prostascint imaging were associated with significant increase in the probability of having recurrent disease. Furthermore 42.8% of patients demonstrated regional uptake in prostatic fossa with or without regional lymph nodes. Almost one-third of patients (30.6%) had local uptake only in the prostatic fossa. These results are in agreement with the known fact that one-third of prostate tumors that recur after prostate surgery occurs locally within the prostatic bed. Thus a positive Prostascint scan results can help classify the patients into two clinically useful categories, i.e.   those with local disease and those with distant recurrent disease, which are candidates for subsequent salvage treatment protocols. Challenges associated with the use of Prostascint imaging   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Imaging with indium In-111 capromab pendetide is technically challenging, requiring high degree of attention to anatomical details, which is not normally necessary with most nuclear medicine studies. The image quality of Prostascint imaging is observed to widely vary among different institutions depending on the method of image acquisition, the skills of the interpreting radiologist, and the resolution of cameras used for SPECT scanning (Wong, Turkington, Polascik, Coleman, 2004). Thus Prostascint imaging requires special training of the involved health care professionals in the field of nuclear medicine, utilizing this technique. Interpretation of the images requires the nuclear medicine physician to become familiar with detailed anatomy of the pelvis in order to read through the normal uptake patterns seen with this drug. On being given sufficient training and experience, the study can become routine for most nuclear medicine departments. Some of the limitations associated with the use of Prostascint scan include, relatively low spatial resolution and low detection efficiency of medium-energy collimators used in the past for detection of In-111 photo peaks; nonspecific localization of monoclonal antibodies in the blood, bowel, bone marrow, and prostate gland and lack of anatomic information on the part of the radiologist to localize accumulation of radiotracer (Wong et al, 2004). In order to improve upon the image quality, diagnostic accuracy and to discover a practical and efficient method of imaging, free from the above described problems, increasing degree of research has been done to improve image resolution. Over the past 5 years, significantly greater image resolution from improved camera technology and the use of co-registration to fuse functional images provided by radioimmunoscintigraphy with anatomic imaging scans such as CT or MRI (Wong, et al 2004). The fusion of these images helps in fusion of anatomical image (obtained on CT or MRI) and physiological image (obtained through Prostascint imaging), thereby considerably improving the resolution of fused image. Keane et al (2006) have reported an accuracy of 83% with fused images. The use of dual-head gamma cameras with a much higher resolution, to co-register the functional single-photon emission tomography (SPECT) image and an anatomic image (CT or MRI) has also made a dramatic difference in prostate cancer detection with the Prostascint imaging (Keane, (2006).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Wong et al (2004) conducted a study in which they tried to improve the diagnostic accuracy of this examination by using hybrid gamma camera–CT technology. Imaging was performed on a dual-head scanner with an integrated CT scanner built onto the same rotating gantry as the camera heads (for SPECT scanning). Wong et al reached the conclusion that evaluation of extraprostatic disease in the pelvis and lower abdomen may also be facilitated by the combined SPECT-CT images. However, the sample size of this study was too small to reach any definitive conclusion. In future, larger well designed, randomized controlled studies are required in order to definitely prove the advantage of this type of scanning in comparison to conventional Prostascint imaging. Safety and precautions Certain precautions which must be observed at the time of Prostascint imaging as   highlighted in a study by Raj et al (2002) are as follows: Prior investigations have demonstrated that 111In-capromab pendetide immunoscintigraphy is safe, with mild adverse effects and minimal increase in the levels of antibodies directed against murine antibody levels (Raj et al, 2002). There is a theoretical risk for occurrence of allergic reactions, including anaphylaxis, in patients who receive murine antibodies. Although serious reactions of this type have not been observed in clinical trials after administration of Indium In-111 Prostascint, Raj et al (2002) have suggested that emergency medications for the treatment of anaphylactic reactions should be available during admin ­istration of this agent. confirmatory trials in the future Due to difficulties in image interpretation, Prostascint imaging is associated with high rate rates of false positive and false negative image interpretation results.   Thus patient management should not be solely based on ProstaScint scan results without appropriate phase three confirmatory trials in the future. Positive Prostascint scan results should be followed by further confirmatory tests (e.g. histopathological analysis). Also these images should be interpreted only by physicians who have had specific training in Indium In-111 Prostascint image interpretation. High False positive scan rates associated with Prostascint may be detrimental to patient care by resulting in inappropriate surgical intervention in patients who had been cured of their primary cancer and have no cancer recurrence. On the other hand, inappropriate denial of curative therapy may occur in case results are not confirmed. Positive Prostascint scanning can also result in inappropriately high stage on sur ­gical staging if only areas of uptake are sam ­pled. Surgical sampling should not be limited to the areas of positive uptake, unless histologic examination Of these areas has yielded positive results Bone scans are more sensitive than Prostascint scanning for the detection of metastases to bone. Thus Prostascint scanning should not replace bone scan for the evaluation of skeletal metastases. Prostascint imaging involves use of radiopharmaceuticals, which must be used only by physicians and other health care professionals who are qualified for handling and using radionuclides. Care should be taken to minimize radiation exposure to patients and medical per ­sonnel, consistent with proper hospital and patient management procedures. Due to delayed clearance of In- 111 Prostascint and post scan localization in the bowel, blood , kidneys, and bladder, most researchers suggest that bladder   should be catheterized and irrigated when obtaining SPECT images. A cathartic must also be administered the evening before imaging the patient, and a cleansing enema should be administered within an hour prior to each imaging session. Conclusion From the above discussion it becomes apparent that Prostascint imaging using indium In-111 capromab pendetide offers important additional information to physicians who treat and manage prostate carcinoma patients. In the patients with primary disease, prostascint imaging should be considered after a definitive diagnosis of cancer has been made, prior to surgery or radiation therapy, when there is high risk for pelvic lymph node metastasis. Prostascint imaging serves as   a reliable, noninvasive means of differentiating patients with organ-confined disease from those with metastatic spread to lymph nodes and complements other indicators of metastatic disease like PSA, Gleason score etc. A positive Prostascint scan serves as an indicator for undertaking confirmatory studies  Ã‚   (biopsy of involved sites) prior to initiation of a definitive surgical procedure. In the modern era, high quality fused images (with CT or MRI) obtained from using higher-resolution gamma cameras, have confirmed the value of radioimmunoscintigraphy. However well designed randomized controlled trials in future are required to prove the exact clinical role of Prostascint imaging in cases of prostate cancer. 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