Compact Gamma Camera for Detection of Prostate Cancer

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1 Compact Gamma Camera for Detection of Prostate Cancer Presented at: Human Interest Panel Federal Laboratory Consortium Annual Conference Nashville, Tennessee Brookhaven National Laboratory and Hybridyne Imaging Technologies, Inc. May 3, 2011

2 Outline: Statement of problem What is used today to detect prostate cancer? Shortcomings of conventional tools Proposed solution Description of advantages over existing instruments Key accomplishments in device development and testing Next steps Summary and conclusions

3 Background and Statement of Problem Background: (1) Two million men living in the U.S. have been diagnosed with prostate cancer; (2) 1 in 6 will develop prostate cancer during their lifetimes, (3) 1 in 35 will die from the disease. Problem: Instruments available today cannot accurately image intra-prostatic cancer, and detection is disappointingly low 1) Undiagnosed prostate cancer is highly prevalent 2) Significant numbers of cancer that could and should be treated at an early stage are missed due to false-negative biopsies 3) Unnecessary surgeries, including radical prostatectomy 4) Recurrent surgery after initial treatment due to inability to effectively localize and treat cancerous tissue 5) Limitations in administering optimal diagnostic and therapeutic procedures (e.g., brachytherapy)

4 What is used today? Ultrasound probe produces high-frequency sound waves that bounce off the surface of the prostate. The sound waves are recorded into video or photographic images of the prostate gland helping urologists estimate the size of the prostate and detect any abnormal tissue.

5 Another example of an ultrasound sonograph Ultrasound sonograph in 2D with prostate in red, the biological tumor volume (BTV) in purple, rectum in brown, and urethra in dark blue. 100% isodose curves are in green, 150% in beige, and 200% in cyan.

6 Trans-rectal ultrasound (TRUS) Principal Shortcoming: Ultrasound cannot differentiate between benign and cancerous tumors Consequences: Insertion of multiple biopsy needles to extract 1-mm diameter tissue specimens required for definitive cancer detection Very low sampling accuracy (low likelihood of a needle hitting a malignant portion of the mm diameter gland) Small cancers are particularly difficult to detect via biopsies For every case of prostate cancer detected by biopsy today, one case is estimated as missed, leading to a medical dilemma regarding re-biopsies in the event of negative biopsy indication and high PSA

7 Approach: The BNL/Hybridyne ProxiScan TM Solution Goal: Develop the first compact digital gamma camera capable of insertion into the rectum as a probe, bringing it directly adjacent to the prostate gland for highresolution localization and imaging of cancer 1) Use CZT detector technology capable of miniaturization and 10x better spatial resolution than conventional (external to body) scintillator-based gamma cameras to reveal small tumors 2) Patient is injected with a radiopharmaceutical tracer with a high specificity for prostate cancer 3) Prostascint (manufactured by Cytogen acquired by Innocoll Pharmaceuticals, Inc.) has a 10:1 uptake in cancer compared to normal tissue, plus it has FDA approval for use in studying the spread of prostate cancer

8 Distinct advantages of ProxiScan Technology Compact, handheld size Capable of trans-rectal measurements, other difficult positions easily accessed, lower cost, and additional pre-operative and intra-operative uses High spatial resolution High image quality, small tumors easily detected and quantified, and easily interpreted Depth information Planar and 3-D images to determine the precise location of the intra-prostatic tumor(s) for accurate positioning and mapping of areas of interest High sensitivity Fast imaging time and reduced concentration of indium-111 radioisotope

9 Applications to Prostate Cancer Detection and Treatment Scanning to detect cancer Scanning to assist in biopsies (perhaps ultimately eliminating or reducing the need for painful biopsies altogether) Scanning to assist with directing treatment Regular post-therapeutic follow-ups

10 CZT GAMMA SPECTROMETERS AND IMAGING ARRAYS Co-Planar Detector Imaging Array

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12 Large scintillator-based external gamma cameras have poor spatial resolution (~12-15 mm) Image fusion for a patient with a ProstaScint scan and CT scan. Increased activity secondary to vascularity is seen in normal structures including the femoral arteries and bone marrow. These signals were used as anatomic landmarks to co-register the ProstaScint and CT images.

13 Improved Localization of Small Tumors and Boundaries C-arm external gamma camera CZT-based gamma camera kev 140 kev FWHM 2.6 % CZT detector Tc-99m + In-111 Number of counts kev FWHM 2.7 % 245 kev FWHM 2.0 % Channel number

14 Direct Conversion of Gamma Energy to Current Leads to Improvements in Energy and Spatial Resolution

15 CZT Multi-Element Pixel Arrays As fabricated With solder mask protecting the pixels prior to PCB bonding Typical Dimensions THICKNESS: 5 mm PIXEL PITCH: 2.5 mm ANODES: 2 mm x 2 mm

16 CZT PCB Module Schematic cross-section of PCB-attached to CZT detector module. Final Product After PCB attachment

17 Bottom side of PCB board Memory for firmware code MWASIC Microcontroller Clock generator

18 Assembled probe PCB board Collimator in shrink tube Cables for power supplies and communication Collimator CZT detectors

19 Pre-clinical Animal Tests Using ProxiScan TM Gamma Camera Tests were carried out at Molecular Insight Pharmaceuticals (Cambridge, MA). Trofex was used for the animal tests. Trofex, which is an I-123 based radiopharmaceutical, was injected into a mouse I-123 emits 159-keV gamma rays ProxiScan s linearity range covers this energy, so the camera was expected to produce images of the uptake of Trofex for a mouse with prostate cancer cells

20 Experiment setup Image Acquisition Computer Probe Mouse Several positions for the mouse were used during the tests.

21 Test results demonstrate high-spatial-resolution imaging Liver Kidney Tumor Measured objects - One kidney and tumor of a live mouse Measurement time - 2 min Measured object size - Kidney: 10.5 mm x 8 mm - Tumor: 11 mm x 5.6 mm Relative activity - 4.6:1 (kidney to tumor) Note: White line is (10%) threshold cut. Image

22 Kidney 1 Kidney 2 Test results (con t) Tumor Measured objects Two kidneys and tumor of a live mouse Measurement time 2 min Measured object size Kidney 1: 13 x 8 mm Kidney 2: 12 x 5 mm Tumor: 7 x 5 mm Relative activity 1.4:1 (kidney 1 to kidney 2) 11:1 (kidney a to tumor) 15:1 (kidney b to tumor)

23 Next Steps: Complete clinical tests at Johns Hopkins Univ. and if needed, complete complementary tests elsewhere 1. Trans-rectal measurements with Prostascint tracer and compare with traditional gamma camera 2. Discovery of new radiopharmaceutical agents 3. Internal review board (IRB) provided approval in January 2011 Novel collimator to provide improved views 1. Design and construct innovative collimator 2. Complete additional tests with animals and phantoms to demonstrate image quality and instrument s impact to other applications Reduce pixel size to further improve spatial resolution New ASIC for more channels, lower power and less noise Work on packaging to improve attractiveness and graphical user interfaces and modify software to improve quantification

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25 Summary and Conclusions: CZT is the change agent 1. Improvement due to proximity & image quality 2. CZT detectors and ASICs take advantage of miniaturization 3. CZT detectors are simple and low maintenance 4. CZT detectors are versatile & high performance Pre-clinical trials look very promising we can build it! FDA 510(k) clearance (for ProxiScan s 2-D camera) received in April 2010 Additional performance enhancements for the compact gamma camera are underway Many new applications (beyond connection to prostate cancer) are enabled by CZT detector technology