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Recent SPECT/CT Imaging Studies using ORNL/JLAB instrumentation

Recent SPECT/CT Imaging Studies using ORNL/JLAB instrumentation. Bethesda May 20, 2005. Overview. Systemic AA-Amyloidosis New contrast agent studies. Serum amyloid P component (SAP) is a normal plasma protein and a universal constituent of amyloid deposits.

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Recent SPECT/CT Imaging Studies using ORNL/JLAB instrumentation

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  1. Recent SPECT/CT Imaging Studies using ORNL/JLAB instrumentation Bethesda May 20, 2005

  2. Overview • Systemic AA-Amyloidosis • New contrast agent studies

  3. Serum amyloid P component (SAP) is a normal plasma protein and a universal constituent of amyloid deposits. I-123 labeled SAP has been used clinically to diagnose and monitor systemic Amyloidosis. ORNL/UT collaboration is the first group to image I-125 labeled SAP in murine Amyloidosis models. Using iodine-labeled SAP as the “gold standard” our goal is to identify new imaging compounds for improved diagnosis and therapy. Motivation

  4. The huIL-6 Transgenic Mouse as a Model of Systemic AA-Amyloidosis • Balb/c mice constitutively express the human IL-6 gene • The mice have high circulating concentrations of sAA (~ 1 mg/mL) and develop severe AA-amyloid disease at 8 mos. of age • Administering amyloid enhancing factor to 8 wk old mice results in severe (usually fatal) pathology within 10 wks post-injection • Amyloid deposits found in spleen, liver, pancreas, kidney, heart, tongue and vasculature

  5. 125I-SAP Co-localizes with AA-Amyloid Deposits in the Mouse Autoradiography- Splenic Amyloid Deposits 125I-SAP Autoradiography - hematoxylin and eosin counterstain (Mag. 160 x) Congo red (Mag. 160 x)

  6. 6 Balb/c huIL-6 mice 3 mice 3 mice Inject with 100 μL PBS Inject with 100 μg AA-AEF Day 0 1% Lugol’s solution as drinking water 1% Lugol’s solution as drinking water Wk 7 – 48 hours 300 μCi 125I-huSAP Wk 7 300 μCi 125I-huSAP Sacrifice and Image Mice Sacrifice and Image Mice Wk 7 + 24 hours Biodistribution & Autoradiography Biodistribution & Autoradiography SAP Imaging Protocol

  7. Dual-Modality Imaging of Mice with AA-Amyloid Axial section through spleen and liver SPECT 3D-SPECT/CT SPECT/CT

  8. Enlarged spleen is a consistent pathology 3D-SPECT/CT

  9. Rendering and Determining Organ Volumes from SPECT Data-sets

  10. % Injected Dose/gram tissue % Counts per organ Comparison of Amyloid Quantitation by Biodistribution and Image Analysis * Image analysis cannot discern the pancreas from the liver which leads to an overestimation of the hepatic deposits and a decrease in the ratio.

  11. Conclusions • 125I-SAP provides high resolution mapping of AA-amyloid in mice using a microSPECT imager. • Amyloid burden can be quantified at various levels of resolution using autoradiography, biodistribution or SPECT image analysis. • CT-directed, 3-dimensional volumetric rendering of the organs will provide organ-restricted specific activities and a greater level of “internal resolution” than the SPECT images alone.

  12. But, • SAP scintigraphy has been criticized for: • Its inability to image cardiac amyloid in AL patients • Its overestimation of hepatic involvement due to its catabolism in the liver • So, • A small proteinase inhibitor, aprotinin, has been evaluated, clinically and compared to SAP SPECT imaging in our model.

  13. 99mTc-Aprotinin Scintigraphy for Amyloidosis J. Nuc. Med. Vol. 44 No. 2 177-183 IgGκ MM Patient Renal AL Patient Plasmacytoma Patient Left sinus Heart Heart Liver Intestine Joints carpal tunnel Tongue and submandibular gland Left femur 86 yr old ♀ 78 yr old ♀ 64 yr old ♂

  14. 1 2 3 1 2 3 SPECT images of 125I-aprotinin in AA-amyloidotic mice- sagital SPECT images of 125I-aprotinin in AA-amyloidotic mice- coronal 125I-Aprotinin SPECT Imaging for AA-Amyloidosis in Mice 125I-Aprotinin is not an efficient tracer for detecting AA-amyloid deposits in our mouse model. However, it can detect renal dysfunction.

  15. Iodine labeled SAP remains the “gold standard” control (20x lower window) control (20x lower window) huIL-6 huIL-6

  16. Contrast agents are required for CT-based image segmentation water soluble contrast agent injected ip

  17. Segmented spleen and liver (CT) vs. SPECT distribution

  18. Open Challenge… Need to “bloat” CT data to capture lower resolution SPECT activity

  19. Newly developed contrast agent specifically targets the spleen and liver

  20. Liver/Spleen contrast agent (in vivo study)

  21. Contrast agent can also be configured as a blood pool agent

  22. In Vivo blood pool imaging study

  23. Summary • SPECT and CT instrumentation are in routine use. • Representative SPECT/CT study of AA amyloidosis model presented. • Recent contrast agent studies presented.

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