(UroToday.com) The 2026 American Society of Clinical Oncology (ASCO) Annual Meeting was host to a kidney and bladder cancers poster session. Dr. Yasser Ged presented a first-in-human study of [111In] XYIMSR-01 SPECT/CT, a novel carbonic anhydrase IX small molecule in patients with metastatic clear cell renal cell carcinoma (RCC).
Clear cell RCC accounts for approximately 75% of renal cancers and is characterized by von Hippel-Lindau (VHL) loss and subsequent overexpression of carbonic anhydrase IX (CAIX). CAIX expression is highly prevalent in ccRCC and has been explored as an attractive target for molecular imaging and radioligand therapy. Existing approaches using radiolabeled antibodies against CAIX have demonstrated successful tumor targeting but are limited by slow pharmacokinetics and delayed imaging requirements. To address these limitations, investigators developed XYIMSR-01, a novel dual-motif, high-affinity, low-molecular-weight CAIX-targeted imaging agent engineered for rapid clearance and high tumor-to-background contrast.
Preclinical studies demonstrated strong tumor uptake, favorable biodistribution, and selective retention in CAIX-expressing ccRCC xenografts, supporting clinical translation. Based on these findings, the current first-in-human study was initiated to evaluate [111In]-XYIMSR-01 SPECT/CT imaging in patients with metastatic ccRCC.
This is an investigator-initiated, single-center, phase I study conducted at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. The primary objectives are to evaluate the safety, tolerability, feasibility, biodistribution, and dosimetry of [111In]-XYIMSR-01 SPECT/CT imaging in patients with metastatic ccRCC. Secondary objectives include assessment of the optimal imaging time point, pharmacokinetic profile, biodistribution, and comparison with conventional imaging modalities.
Eligible patients must have:
- Histologically confirmed metastatic ccRCC
- At least two measurable metastatic lesions, each measuring ≥1.5 cm
- Treatment-naïve metastatic disease
- Adequate organ and bone marrow function
- No prior radioisotope administration within five biological half-lives before study drug injection
The study schema includes screening within 30 days prior to imaging, followed by a single intravenous administration of [111In]-XYIMSR-01 (9.5 ± 1.0 mCi). Serial SPECT/CT imaging is performed at approximately 2–4 hours, 24 ± 1 hours, and 48 ± 1 hours after administration. Blood samples are collected at multiple time points to support biodistribution, dosimetry, pharmacokinetics, and safety analyses. Imaging analyses and physiologic assessments are subsequently performed.![The study schema includes screening within 30 days prior to imaging, followed by a single intravenous administration of [111In]-XYIMSR-01 (9.5 ± 1.0 mCi). Serial SPECT/CT imaging is performed at approximately 2–4 hours, 24 ± 1 hours, and 48 ± 1 hours after administration. Blood samples are collected at multiple time points to support biodistribution, dosimetry, pharmacokinetics, and safety analyses. Imaging analyses and physiologic assessments are subsequently performed.](/images/com-doc-importer/273-asco-2026/asco-2026-first-in-human-study-of-111in-xyimsr-01-spect-ct-a-novel-carbonic-anhydrase-ix-small-molecular-in-patients-with-metastatic-clear-cell-rcc/image-0.jpg)
At the time of reporting, the study had enrolled 10 patients. Investigators noted that whole-body planar and SPECT/CT imaging successfully visualized metastatic lesions with favorable tumor-to-background contrast.
The figure below demonstrates a clear visualization of a metastatic lesion with marked radiotracer uptake. Quantitative analysis demonstrated a lesion maximum standardized uptake value (SUVmax) of 4.8 compared with a liver SUVmax of 1.4, corresponding to a lesion-to-liver uptake ratio of approximately 3.4. These findings support selective accumulation of [111In]-XYIMSR-01 within metastatic ccRCC lesions and provide early evidence of favorable imaging characteristics.![The figure below demonstrates a clear visualization of a metastatic lesion with marked radiotracer uptake. Quantitative analysis demonstrated a lesion maximum standardized uptake value (SUVmax) of 4.8 compared with a liver SUVmax of 1.4, corresponding to a lesion-to-liver uptake ratio of approximately 3.4. These findings support selective accumulation of [111In]-XYIMSR-01 within metastatic ccRCC lesions and provide early evidence of favorable imaging characteristics.](/images/com-doc-importer/273-asco-2026/asco-2026-first-in-human-study-of-111in-xyimsr-01-spect-ct-a-novel-carbonic-anhydrase-ix-small-molecular-in-patients-with-metastatic-clear-cell-rcc/image-1.jpg)
Overall, this first-in-human study establishes the feasibility of CAIX-targeted SPECT/CT imaging using [111In]-XYIMSR-01 in metastatic ccRCC. The agent's rapid pharmacokinetics, favorable biodistribution profile, and high tumor-to-background contrast support continued clinical development as a potential imaging biomarker platform and future theranostic companion for CAIX-directed strategies in renal cell carcinoma.
Presented by: Yasser Ged, MBBS, Medical Oncologist, Johns Hopkins Medicine, Baltimore, MD, USA
Written by: Rashid K. Sayyid, MD, MSc, Assistant Professor, Urologic Oncologist, Department of Urology at The University of Arizona and Banner University Medical Center, Tucson, AZ – @rksayyid on X during the American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting held in Chicago, IL between May 29th and June 1st, 2026