Associated Lab Members
Dr. Cheal graduated from the University of California at Davis in 2008. After completing postdoctoral research fellowships at the National Institutes of Health and Memorial Sloan Kettering Cancer Center (MSKCC), she transitioned to Senior Research Scientist at MSKCC in 2014 in the laboratory of Steven Larson MD. In 2022, she joined Radiology Department at Weill Cornell Medicine as a faculty member. Her research is centered on the translational development of molecularly targeted radiotheranostics for treatment of solid tumors, with an emphasis on radioimmunotherapy with alpha- and beta- emitting radionuclides. Her research is supported, in part, by the National Cancer Institute.
Areas of Specialization: Radioimmunotherapy, immunoPET, radiochemistry, multi-step drug delivery, molecular imaging (PET and SPECT)
Applications: Cancer Diagnosis and Treatment (colorectal, breast, ovarian, neuroblastoma)
Dr. Rinne earned her doctorate in Medicinal Chemistry from Uppsala University (2022). During her doctoral training, she developed diagnostic and therapeutic approaches for targeting of human epidermal growth factor type 3 (HER3) in cancer. She is an expert in the radiosynthesis and preclinical characterization of theranostic radiopharmaceuticals (peptides, engineered scaffold proteins, antibodies). In 2022, she joined Dr. Cheal’s lab at the Radiology Department of Weill Cornell Medicine as a Postdoctoral Research Scientist. Her current focus is on the development of novel pretargeted radioimmunotherapy regimens using alpha- and/or beta-emitting radionuclides.
Niloufar obtained her MD from Shahid Beheshti University of Medical Sciences, Tehran, Iran, in 2020. During medical school, she contributed to clinical, translational, and basic science research projects. In 2022, she joined the Departments of Surgery and Radiology at Weill Cornell Medicine as a Postdoctoral Research Fellow. She is an aspiring surgeon-scientist dedicated to bridging the gap between clinical practice and research, with expertise in preclinical characterization of experimental therapeutics, including chemotherapies and radiopharmaceuticals. In the Cheal lab, her research focuses on exploring innovative molecularly targeted radiopharmaceuticals for treating gastric and colorectal cancers.
Dr. Ruder obtained his MD from McGovern Medical School at Houston (Formally University of Texas Houston) in 2017. After completing an Internal Medicine Residency at Mount Sinai Icahn School of Medicine in 2020, he served as a Hospitalist/Clinical Instructor at Department of Medicine, Elmhurst Hospital NYCHHC, Queens, NY and at Department of Medicine, Mount Sinai Icahn School of Medicine. In 2022, he joined the Division of Hematology and Oncology, New York Presbyterian – Weill Cornell Medical Center as a Clinical Fellow. His current focus is on the development of novel immunoPET and radioimmunotherapy regimens for treating advanced prostate cancer (in collaboration with Scott Tagawa MD).
Dr. Ambika P. Jaswal joined the Sarah Cheal Lab as a Postdoctoral Associate in September 2024. She holds an MS in Nuclear Medicine from Punjab University, Chandigarh, India, and earned her Ph.D. in Life Sciences from INMAS DRDO, Delhi, India. Her doctoral research focused on the synthesis, characterization, and preclinical evaluation of small molecule based radioprobes for targeted imaging and therapy of various tumors using Tc-99m, Ga-68, F-18, C-11, and Re-188. Her doctoral research experience in radiochemistry and radiopharmacy laid the foundation for her specialization in radiation theranostics. Prior to joining the Sarah Cheal Lab, Dr. Jaswal completed her first postdoctoral training at UPMC, Children’s Hospital of Pittsburgh, University of Pittsburgh, from September 2021 to August 2024. During this period, she concentrated on the development of antibody and antibody-fragment-based targeted Radioimmunoprobes for theranostic applications in central nervous system (CNS) tumors and colorectal tumors using Zr-89, In-111, Ac-225 and Lu-177.
Sayani Saha is a research technician I in the laboratory of Dr. Sarah M. Cheal, Assistant Professor of Biological Chemistry in Radiology, MI3, Department of Radiology, Weill Cornell Medicine. Sayani graduated with a Master of Biotechnology from Northwestern University with a passion for cancer research and theragnostic. Sayani worked at Blue Rock Therapeutics on macrophage repolarization in the tumor microenvironment of glioblastoma which drove her into the world of oncology. She has experience with working in cell culture and pursuing her interest of becoming an expert in radiotherapy and cancer immunology.
Curative therapy is a major need in solid human tumors of adults and children. Conventional radioimmunotherapy with tumor-targeting antibodies conjugated with radionuclides suffers from poor therapeutic index (TI). We use a multi-step approach to RIT called “pretargeted RIT” to improve TI by combining the desirable tumor-targeting features of antibodies with the ideal pharmacokinetics of small-molecule radiohaptens.
Fig 1. from PMID: 36215514 Conventional RIT (left) versus 3-step pretargeted RIT (center) versus 2-step pretargeted RIT (right). During conventional RIT, a radioimmunoconjugate is administered. Radioactive payload is specifically targeted to tumor, but at the expense of concurrent off-target exposure to normal tissues. During 3-step pretargeted RIT, a non-radioactive anti-tumor antigen/anti-radiohapten bispecific antibody (BsAb) is administered, followed the next day with a clearing agent to rapidly reduce circulating (i.e., not tumor bound) BsAb. After a few additional hours, a radiohapten is administered which is captured by intratumoral BsAb or otherwise efficiently cleared via the renal route. This dramatically reduces off-target exposure of radioactive payload. During 2-step pretargeted RIT, an innovative BsAb platform called “SADA” (self-assembling and disassembling) can be applied to eliminate the requirement of a clearing agent. PMID: 32958698
We strive to develop theranostic (therapy/diagnostics) PRIT with beta- or alpha-emitting radioisotopes to enable personalized dosimetry and treatment planning. In an approach we call “DOTA-PRIT” short for “1,4,7,10-tetraazacyclododecane-N, N’, N’’, N’’’-tetraacetic acid (DOTA)-based PRIT” we first administer a non-radioactive anti-tumor/anti-DOTA hapten bispecific antibodies to “pretarget” the tumor, followed by administration of a radioactive-DOTA-hapten.
Fig 2. Nude mice bearing established GPA33-expressing SW1222 human colorectal xenografts (lower flank) undergoing GPA33-targeted DOTA-PRIT with a 177Lu-DOTA-radiohapten. GPA33 is a cell-surface marker expressed on >95% of colon cancers. 177Lu has both beta particle emissions for therapy and gamma emissions for imaging. SPECT/CT images were performed at 24 hours post-injection of 177Lu-DOTA-radiohapten using a dedicated small-animal SPECT/CT scanner. Based on image analysis, the 177Lu-uptakes in tumor and kidney were 9.42 %ID/g and 0.72 %ID/g, respectively, giving a tumor-to-kidney activity ratio of 14. Collectively, these data suggest highly favorable TIs during therapy. PMID: 28705917
We have also extended the approach to actinium-225 (225Ac), an alpha-emitting isotope. Please see PMID: 33052220
We recently applied this approach to treat aggressive intraperitoneal ovarian cancer with 225Ac-radiohapten. Please see PMID: 37348919
Sponsored by Y-mAbs Therapeutics, Inc. the SADA platform + 177Lu-DOTA is currently being investigated in a phase I clinical trial for the treatment of certain GD2-positive solid tumors, including small cell lung cancer, sarcoma and malignant melanoma. Please see NCT05130255
Radiopharmaceutical therapy (RPT) has incredible potential to be a first-line therapy for multiple cancer indications. During RPT, a therapeutic radionuclide is localized specifically in malignant tissue to directly deliver ionizing radiation. To enhance patient-specific dosimetry and treatment planning, whole-body molecular imaging (PET or SPECT) can be used to assess the extent of tumor targeting. Despite its enormous promise, the theranostic RPT approach has produced objective responses in only 30-60% of patients. In solid tumors, the potential for cures is limited by the low therapeutic indices (TIs) achievable with common targeting vectors. Engineered bacterial therapies have extraordinarily high tumor-to-normal tissue accumulation ratios without the requirement of a tumor-specific surface antigen target (i.e., epitope-independent tumor-tropism), especially to key radiosensitive issues that are dose-limiting (red bone marrow and kidney).
Fig 3. Salmonella are safe and preferentially accumulate in tumors. A) Biodistribution in BALB/c mice, 14 d after IV injection of 1×107 Salmonella. Bacterial densities in the spleen and liver were 3000 times lower than in tumors (***, P = 0.0001; n = 5). Densities were below detection in lungs, kidneys, hearts and brains. This accumulation pattern is the basis for high therapeutic index. B) As soon as three hours after injection, bacteria preferentially accumulated in tumors over livers. The relative density grew to 4,600 by 72 h. C,D) Comprehensive hematology (C) and chemistry profiling (D) showed no differences in the number of immune cells and no liver damage (ALP, alkaline phosphatase; ALT, alanine transaminase; and AST, aspartate transaminase) compared to saline controls.
Our central hypothesis is that tumortropic Salmonella can be genetically engineered with bioorthogonal markers for imaging and therapy.
ImmunoPET combines highly specific monoclonal antibodies (mAb) with PET imaging (frequently the radiometal 89Zr, t½ = 3.3 days). As evidenced by the dozens of clinical-stage probes, immunoPET is emerging as a valuable molecular imaging tool in oncology. For the imaging and treatment of advanced prostate cancer, the humanized mAb J591, which binds prostate-specific membrane antigen (PSMA) on the surface of epithelial prostate cancer, has been used as a carrier for radionuclides (for immunoPET: 89Zr-J591 or 124I-J591; for radioimmunotherapy: 177Lu-J591 or 225Ac-J591) and cytotoxic drugs (maytansinoid DM1 or monomethyl auristatin E).
Fig 4. 89Zr-huJ591 immuno-PET imaging in patients with advanced metastatic prostate cancer. Serial whole-body 89Zr-huJ591 scans (MIP images). Images show physiological distribution in cardiac and vascular blood pool, decreasing with time, in liver, spleen, kidneys, and GI tract. Images show increased accumulation in multiple bone lesions, best seen in day 8 image. Many of these lesions are not clearly visualized on 99mTc-MDP scan (right). PMID: 25143071
We strive to develop novel immunoPET agents for advanced prostate cancer, with an emphasis on biomarker targets alternative to PSMA and diagnostic surrogates for radioimmunotherapy with 225Ac-huJ591.
(1) Bispecific antibody-based imaging probes (86Y, 111In; development ongoing: 68Ga, 89Zr) against GD2, HER2, GPA33 antigens. Other antigen targets reported: CD38, CD45, CD20, CEA.
(2) Bispecific antibody-based therapy probes (177Lu, 225Ac; development ongoing: 212Pb) against GD2, HER2, GPA33 antigens. Other antigen targets reported (90Y): CD38, CD45, and CD20.
(3) 89Zr-labeled monoclonal antibodies (in development: 89Zr-CEACAM5 mAb)
NIH R01 CA233896 (PI), NIH R37 CA262557 (co-I), WCM Prostate SPORE Career Enhancement Program Award November 2023-October 2024 (PI).
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