Slide 1: Authors: Titz, Grudzinski, Stilp, Jaskowiak, Rice, Weichert, Kuo
Benjamin Titz, Joseph Grudzinski, Emmaline Stilp, Christine Jaskowiak, Stephanie Rice, Jamey Weichert, John Kuo
Slide 2: Funding and disclosures
NIH/NCI: 1 R01 CA158800 (PI: Hall/ Weichert ) UW ICTR from NIH/NCATS: UL1TR000427 (PI: Hall) UW Carbone Cancer Center from NIH/NCI: P30CA014520 (PI: Hall) Lance Hall -- No financial COI Physician sponsor of IND for 124 I - CLR1404 Jamey Weichert – inventor of CLR1404 and founding member of Cellectar
Slide 3: Unmet needs in brain tumor imaging
Incomplete delineation of tumor infiltration Affects surgical resection & XRT planning & survival Non - specificity for tumor vs necrosis or edema Biopsy site planning & resection of eloquent brain Differentiating tumor recurrence from pseudoprogression (PP) Huge problem w/ Temozolomide & newer agen
Slide 4: Phospholipid ether (PLE) analog
Phospholipid ether (PLE) analog Enters malignant cells via membrane lipid rafts Over expressed in malignant cells (6 – 10x) Tumor specific uptake & prolonged retention in >50 preclinical models Including gliomas Isoteric iodine substitution 124 I - for molecular/PET imaging 131 I - for therapy Optic
Slide 5: Lipid Rafts
Lipid Rafts Cholesterot Extracellular Giycosphyngolipia | Peri Ttit Sesesssegy UU Lipid rafts are specialized microdomains of plasma membrane that are enriched in cholesterol and glycosphingolipids Lipid rafts serve as molecular platforms that spatially organize molecules for specific signaling path
Slide 6: Diapeutic Phospholipid Ether Analogs
Diapeutic Phospholipid Ether Analogs 131 I - CLR1404 radioactive therapeutic + Cancer stem cell 124 I - CLR1404 radioactive diagnostic+ Cancer stem cell 127 I - CLR1404 non - radioactive therapeutic CLR1501 fluorescent diagnostic CLR1502 fluorescent diagnostic (Near IR) Complete safety pharmacology
Slide 7: Tumor uptake across xenograft and spontaneous models
Pancreas Adrenal Prostate Prostate Colon (3) Prostate Bladder COLON TN Breast Pancreas Prostate Breast Colon Brain Brain Saracoma Primary+Mets in 55/57 xenograft and spontaneous models Human Colorectal Lung Met
Slide 8: Study objectives
Describe first successful use of 124 I - CLR1404 in humans with brain tumors Avidity in brain tumors SUV and Tumor to Background Ratios Compare PET and MRI Tumor volumes Concordant and d iscordant tumor regions
Slide 9: Study design and methods
16 pts with brain tumors 1 new dx (WHO Gr IV) 11 previously tx’d gliomas (WHO Gr II – IV) 3 previously tx’d metastases 1 previously tx’d medulloblastoma 2 or 5 mCi (74 or 185 MBq ) 124 I - CLR1404 iv PET/CT at 6 - , 24 - , and 48 - hours after injection 2D, list - mode, 90 minutes per scan Qualitati
Slide 10: Imaging results summary
No uptake in normal brain Uptake in major vascular structures Not in all areas of breakdown of BBB 12/16 pts had avid tumor uptake 4 pts w/ recurrence vs PP had no uptake Tumor uptake typically increases over time Both areas of concordant & discordant PET uptake and MRI enhancement
Slide 11: Glioma (recurrent vs PP) PET-MR
é Tif Glioma (recurrent vs PP) PET-MR
Slide 12: WHO Gr IV Glioma (recurrent vs PP)
Slide 13: Slide 13
Slide 14: Glioma (Recurrent vs PP)
1ioma (Recurrent vs PP)
Slide 15: Gr III Glioma (Recurrent vs PP)
Gr Il Glioma (Recurrent vs PP) Ir ~
Slide 16: Contrast MRI, 124I-NM404 PET, FDG-PET
Contrast MRI 124I - NM404 PET FDG - PET Brain met clearly seen on NM404 PET Brain met not seen on FDG PET
Slide 17: Segmented volume
Segmented volume [mL] 100 —m- 01s —@—02_EB —A— 06_D-H —¥—07_SKA —@ 09_K-R —4-10_6-p —P>— 02_JEF —@— 04_s-A —*— 05_SEE —@—06_BAT MRI+ T:B 1.6 T:B 2.0 SUV 1.0 SUV 1.2
Slide 18: Tumor-to-background ratio (T:B)
Tumor-to-background-ratio (T:B) 161 T:B,,, 24hr T:B,, 48hr ce 144 TB... 24hr * T:B,,,, 48hr 755 ¢ 124 104 b EI) 4 Oo 50% 8+ eS ° 64 K tee 25% © & 75% Sa 44 t rp? ose eo . * 5 at, ha 2 ai 1 as oO T T T T T:B,24hr = TB, 48hr = TB, 24hr TB 48hr ave ave ax ax
Slide 19: Conclusions
124 I - CLR1404 successfully images primary and metastatic brain tumors in humans PET tumor volumes larger than MRI + Gad There is significant tumor to background uptake and prolonged retention Additional functional tumor info provided Potential for use as its own biomarker for targeted molecular ra
Slide 20: University of Wisconsin
University of Wisconsin School of Medicine and Public Health