Data Presented At SNM Meeting Demonstrate New Potential For PROSTASCINT(R) Through Advances In Nuclear Medicine Imaging

Cytogen Corporation (Nasdaq: CYTO) today announced the presentation of data from a series of studies with PROSTASCINT(R) (capromab pendetide), the first and only commercial monoclonal antibody-based agent that targets prostate-specific membrane antigen (PSMA) to image the extent and spread of prostate cancer. Results were presented at the 53rd Society of Nuclear Medicine (SNM) annual meeting taking place this week in San Diego, California.

"Advances in nuclear medicine imaging, such as the integration of anatomical and functional imaging, hastened the growth and widespread adoption of positron emission tomography (PET) imaging," said Michael D. Becker, president and chief executive officer of Cytogen. "Similar advances are now being utilized in SPECT imaging with novel molecular imaging agents such as PROSTASCINT as evidenced by the improved imaging quality reported by multiple centers at the SNM meeting. As with PET, these advances show the potential of fusion imaging with PROSTASCINT to improve outcomes for patients and demonstrated important technical and clinical advantages. We will continue to build on the role of PROSTASCINT as the backbone of our prostate-specific membrane antigen (PSMA) platform while driving our clinical development programs in therapeutic indications, such as CYT-500 for the treatment of hormone-refractory prostate cancer."

Fusion imaging with PROSTASCINT, or hybrid imaging, is an in vivo diagnostic technique that combines anatomic images with functional images. Anatomical information derived from either computed tomography (CT) or magnetic resonance (MR) imaging can be fused (or co-registered) with functional information obtained using single-photon emission computed tomography (SPECT) and novel molecular imaging agents, such as PROSTASCINT. SPECT imaging focuses on metabolic abnormalities that may be present earlier than the anatomical changes otherwise seen with CT or MR imaging alone. Co- registering anatomic and functional images provides an anatomic context for areas of enhanced or abnormal uptake, helping physicians identify areas of disease through enhanced image quality thereby enabling them to better plan an individualized treatment protocol for patients.

Highlights of the eight abstracts regarding fusion of PROSTASCINT scans with anatomical images provided by CT or MRI and new advanced image processing methods presented at the SNM meeting include:

"PROSTASCINT SPECT image quality is significantly improved by implementation of 3D OSEM with resolution recovery and attenuation and scatter correction (Abstract # 1436)"

The objective of this study was to determine if PROSTASCINT image quality can be significantly improved by applying resolution recovery techniques while simultaneously reducing image acquisition times.

PROSTASCINT studies were obtained on twelve consecutive patients and images were processed using filtered back projection (FBP), standard 3D-OSEM, and with software processing technology. The software implements a matched filtering technique to control noise, even when iterating enough to recover image features that are not obvious with standard processing. The full, three quarter and half count image sets reconstructed with the software were compared to the full count images processed with FBP and 3D-OSEM. In three patients who also had pelvic CT scans, the CT data sets were used to generate attenuation maps and attenuation correction (AC) and scatter correction (SC) were applied.

On subjective evaluation, software processing significantly improves the resolution and quality of PROSTASCINT images. CT attenuation and scatter correction provide further improvement. Software-processed images using half the total number of counts appeared superior to images processed with FBP and images using 75% of the counts were superior to images processed with 3D-OSEM. These findings suggest use of software processing would make it possible to significantly shorten acquisition times without compromising image quality.

"The advanced image resolution recovery techniques we evaluated using PROSTASCINT images allow physicians to visualize in greater detail the location and extent of disease, from both an anatomical and physiological perspective," said Michael Haseman, M.D., Nuclear Medicine physician with Radiological Associates of Sacramento in Sacramento, California one of the authors of the study. "These advances have the potential to simultaneously increase productivity for physicians and benefit patients by decreasing the amount of time for acquisition of a PROSTASCINT image."

"Improved disease detection with fusion of PROSTASCINT scans and multidetector CT (Abstract # 1040)"

Investigators from the Medical University of South Carolina reported results from one hundred and forty prostate cancer patients who underwent studies that combined the functional images from PROSTASCINT with the anatomic images provided by a multidetector CT. Their experience demonstrated that this combination provided increased specificity and sensitivity for delineation of residual prostate activity and blood vessels from lymphadenopathy and metastatic disease. Furthermore, the use of the multidetector CT decreased the number of required imaging sessions because it eliminated the need to use dual isotopes for determination of blood pool concentration.

"Retrospective diagnostic analysis of localized prostate cancer comparing needle core biopsy results to PROSTASCINT/SPECT fused with CT (Abstract # 1699)"

Investigators from the University Hospitals of Cleveland reported results from a retrospective analysis comparing fusion imaging with PROSTASCINT to needle core biopsy (NCB) results. Statistical analysis demonstrated agreement between NCB and PROSTASCINT. As expected, NCB identified a larger percentage of patients with disease than did PROSTASCINT, with PROSTASCINT sensitivity = 0.735. Since PSMA expression correlates with the aggressiveness of the tumor, the fact that 38% of patients in the study had Gleason scores below six may be causal in having inflated the PROSTASCINT rate of false negatives. These results indicate that localized prostate cancer diagnosis with PROSTASCINT may be utilized as an adjunct to NCB methods for identification of extracapsular extension, seminal vesicle with or without bladder involvement, and metastatic disease in other areas; and may prove particularly useful for the diagnosis of disease at sites where NCB cannot be safely performed.

"Unusual prostate metastasis to the brain: PROSTASCINT, CT, and MRI findings (Abstract # 1052)"

In a report from Yale New Haven Hospital, researchers presented a case of a solitary cerebral metastatic deposit detected by a PROSTASCINT scan in a patient with central nervous system symptoms whose only established malignancy was prostate carcinoma. CT and magnetic resonance imaging (MRI) demonstrated an abnormality corresponding to the same area of increased signal intensity with PROSTASCINT. The presence of cancer at the PROSTASCINT avid site was confirmed by biopsy.

"This is another instance corroborating the value of fusion imaging with PROSTASCINT," said Michael J. Manyak, MD, urologist and vice president of medical affairs for Cytogen. "Cerebral metastases from prostate cancer are unusual, but the strong correlation of fusion imaging with PROSTASCINT with clinical outcomes suggests that we now may be able to detect such unusual metastatic deposits."

"Hybrid imaging with single photon emission and x-ray computed tomography: Initial experience with 332 patients using an integrated 16-slice high-speed CT with a dual head SPECT device (Abstract # 1106)"

The integration of CT with positron emission tomography (PET) has already provided important technical and clinical advantages. New hybrid SPECT-CT devices (with high-speed CT) have been developed. The goal of this study by researchers at the Baptist Hospital of Miami is to relate the initial clinical applications and utilization patterns, and to describe the challenges and successes in implementing this new technology. Of one hundred and thirty general nuclear medicine procedures, nine were fusion imaging with PROSTASCINT performed using a 16-slice high-speed CT device coupled to a state-of-the-art dual-head nuclear imaging device. The study concluded that SPECT/CT fusion provides similar interpretive benefits as is afforded with hybrid PET/CT. In several clinical settings, the availability of CT can shorten image acquisition time and complexity.

"An eigenvalue based similarity measure and its application to tumor detection in nuclear medicine (Abstract # 1427)"

The objective of this study by researchers at King's College Hospital in London is to automatically detect significant differences between images acquired at either different times or with different radioisotopes for the purpose of automated tumor detection. In this approach, two co-registered sets of images are compared. One is assumed to be a tumor free reference data set, while the second image set may contain sites of abnormal PROSTASCINT uptake. Automated methods were used to assess degrees of change between the two sets of images. This approach to change detection is well suited to detecting small localized sites of uptake as demonstrated in detecting lymph node involvement in prostate cancer imaging using PROSTASCINT. The application of a locally adaptive eigenvalue based approach to change detection provides a sensitive and responsive approach to local image change detection and hence to tumor detection.

"Evaluation of quantitative image reconstruction methods for maximum lesion detectability in In-111 ProstaScint(R) prostate SPECT (Abstract # 347)"

The objective of this study by researchers at Johns Hopkins University and GE Healthcare with support from a DOD Idea Award and GE Research Grant, is to evaluate different quantitative image reconstruction methods for maximum lesion detectability with PROSTASCINT. Three distributions of uptake ratios in different organs in the abdomen and pelvical region, elliptically-shaped lesions of two different sizes (10x10x15 and 12x12x17 mm3) and lesion-to- background contrasts of 5:1 and 8:1 were used in a computer generated 3D NCAT phantom to simulate variations found in a patient population. Projections datasets were reconstructed using iterative OS-EM image reconstruction methods with four subsets and with different compensation methods: (1) no compensation, (2) with attenuation compensation (AC), (3) with AC and collimator-detector response (DC) compensation and (4) with AC, DC and scatter compensation (SC). Using optimum iteration numbers and cutoff frequencies statistically significant differences are found between all AUC curves except for those between the reconstruction methods (3) and (4). Results from the study indicate the clinical utility of quantitative image reconstruction methods for maximum lesion detectability with PROSTASCINT.

"Study of iterative SPECT corrective reconstruction methods for lesion detection and localization in In-111 PROSTASCINT imaging by means of combination of Monte-Carlo simulations and clinical evaluation techniques (Abstract # 540)"

Low contrast lesion detection is the main diagnostic task in prostate cancer imaging. The objective of this study by researchers at Johns Hopkins University with support GE Healthcare Research is to evaluate diagnostic properties of PROSTASCINT images obtained with corrective reconstruction techniques. Thirty clinical PROSTASCINT fusion imaging data sets acquired with routine protocol and found negative after clinical examination were used in this study. Patient specific attenuation maps acquired with low resolution CT (slice thickness of 1cm) were re-sliced to match the PROSTASCINT data. Three reconstruction strategies were compared: (1) OS-EM with attenuation compensation (AC) and post-filter parameters currently used at JHU for processing of PROSTASCINT studies, (2) OS-EM with AC and scatter compensation (SC), (3) OS-EM with AC, SC and geometric response (GRC) compensation and (4) RBI-MAP-EM with AC, SC and GRC. Three experienced clinicians participated in the study. One participant identified up to four possible lesion locations for each dataset using Xeleris(TM) (GE Healthcare, Waukesha, WI). The remaining observers reviewed combined images with lesions using Xeleris workstation. Reconstructed lesion contrast with options (2)-(4) was superior to the current clinically used OS-EM AC method. Inclusion of scatter and collimator-detector response modeling into iterative reconstruction were beneficial for lesion detection and localization in the context associated with PROSTASCINT.

About Prostate Cancer

Prostate cancer is the most common type of cancer found in American men, other than skin cancer. In 2006, the American Cancer Society estimates that there will be about 234,000 new cases of prostate cancer in the United States and that about 27,000 men will die from the disease. It is estimated that there are more than 2 million American men currently living with prostate cancer. Tests to determine the amount of prostate-specific antigen (PSA), a protein produced by the cells of the prostate gland, in the blood along with a digital rectal exam is used to help initially detect prostate cancer and is also used to monitor patients with a history of prostate cancer to see if the cancer has come back, or recurred. PSA levels cannot directly identify the extent or location of disease.

About PROSTASCINT

Cytogen's PROSTASCINT molecular imaging agent is the first and only commercial product targeting PSMA. PROSTASCINT consists of a monoclonal antibody (7E11.C5.3) directed against PSMA that is linked to the imaging radioisotope Indium-111. By targeting PSMA, the PROSTASCINT molecular imaging procedure can detect the extent and spread of prostate cancer using a standard gamma camera.

Cytogen is also developing CYT-500, a therapeutic product candidate using the same monoclonal antibody from PROSTASCINT combined with a higher affinity linker to attach a therapeutic as opposed to an imaging radionuclide. CYT-500 is designed to enable targeted delivery of a cytotoxic agent to PSMA- expressing cells. Cytogen expects to begin the first U.S. Phase I clinical trial of CYT-500 in patients with hormone-refractory prostate cancer during 2006.

PROSTASCINT is indicated as a diagnostic imaging agent in newly diagnosed patients with biopsy-proven prostate cancer, thought to be clinically localized after standard diagnostic evaluation and who are thought to be at high risk for pelvic lymph node metastases. PROSTASCINT is also indicated as a diagnostic imaging agent in post-prostatectomy patients with a rising PSA and a negative or equivocal standard metastatic evaluation in whom there is a high clinical suspicion of occult metastatic disease.

A copy of the full prescribing information for PROSTASCINT, including warnings, precautions, adverse events and other safety information, may be obtained in the U.S. from Cytogen Corporation by calling toll-free 800-833- 3533 or by visiting the Web site at http://www.cytogen.com, which is not part of this press release.

About PSMA

PSMA is a protein abundantly expressed on the surface of prostate cancer cells, with an increased expression in high-grade cancers, metastatic disease and hormone-refractory prostate cancer. PSMA is also present at high levels on the newly formed blood vessels, or neovasculature, needed for the growth and survival of many solid tumors. In contrast to other prostate-related antigens such as prostate-specific antigen (PSA), prostatic acid phosphatase (PAP) and prostate secretory protein, PSMA is a membrane glycoprotein that is not secreted. These unique attributes make PSMA an excellent target for monoclonal antibody diagnostic and therapeutic options in prostate and potentially other cancers. Clinical studies have also demonstrated that overexpression of PSMA determined by immunohistochemical staining using the 7E11.C5.3 antibody in primary prostate cancer not only correlates with other adverse traditional prognostic factors, but can independently predict disease recurrence.

ABOUT CYTOGEN CORPORATION

Founded in 1980, Cytogen Corporation of Princeton, NJ, is a biopharmaceutical company dedicated to improving the lives of patients with cancer by acquiring, developing and commercializing innovative molecules targeting the sites and stages of cancer progression. Cytogen's marketed products include QUADRAMET(R) (samarium Sm-153 lexidronam injection), PROSTASCINT(R) (capromab pendetide) kit for the preparation of Indium In-111 capromab pendetide, and SOLTAMOX(TM) (tamoxifen citrate, oral solution 10mg/5mL) in the United States. Cytogen's development pipeline consists of CYT-500, a therapeutic radiolabeled antibody targeting prostate-specific membrane antigen (PSMA), a protein highly expressed on the surface of prostate cancer cells and the neovasculature of solid tumors. Cytogen also has exclusive United States marketing rights to COMBIDEX(R) (ferumoxtran-10) for all applications, and the exclusive right to market and sell ferumoxytol (previously Code 7228) for oncology applications in the United States. Full prescribing information for the Company's products is available at http://www.cytogen.com or by calling 800-833-3533. For more information, please visit the Company's website at http://www.cytogen.com, which is not part of this press release.

ABOUT ROYAL PHILIPS ELECTRONICS

Royal Philips Electronics of the Netherlands is one of the world's biggest electronics companies and Europe's largest, with sales of $37.66 Billion (EUR 30.3 billion) in 2004. With activities in the three interlocking domains of healthcare, lifestyle and technology and 161,100 employees in more than 60 countries, it has market leadership positions in medical diagnostic imaging and patient monitoring, color television sets, electric shavers, lighting and silicon system solutions. News from Philips is located at http://www.philips.com/newscenter.

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