Abstract
[111In]In-XYIMSR-01 is a promising single-photon emission computed tomography (SPECT) imaging agent for identification of tumors that overexpress carbonic anhydrase IX. To translate [111In]In-XYIMSR-01 to phase I trials, we performed animal toxicity and dosimetry studies, determined the maximum dose for human use, and completed the chemistry, manufacturing, and controls component of a standard regulatory application. The production process, quality control testing, stability studies, and specifications for sterile drug product release were based on United States Pharmacopeia chapters <823> and <825>, FDA 21 CFR Part 212. Toxicity was evaluated by using nonradioactive [113/115In]In-XYIMSR-01 according to 21 CFR Part 58 guidelines. Organ Level INternal Dose Assessment/EXponential Modeling (OLINDA/EXM) was used to calculate the maximum single dose for human studies. Three process validation runs at starting radioactivities of ~800 MBq were completed with a minimum concentration of 407 MBq/ml and radiochemical purity of ≥99% at the end of synthesis. A single intravenous dose of 55 μg/ml of [113/115In]In-XYIMSR-01 was well tolerated in male and female Sprague–Dawley rats. The calculated maximum single dose for human injection from dosimetry studies was 390.35 MBq of [111In]In-XYIMSR-01. We have completed toxicity and dosimetry studies as well as validated a manufacturing process to test [111In]In-XYIMSR-01 in a phase I clinical trial.
Original language | English (US) |
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Pages (from-to) | 243-250 |
Number of pages | 8 |
Journal | Journal of Labelled Compounds and Radiopharmaceuticals |
Volume | 64 |
Issue number | 6 |
DOIs | |
State | Published - May 30 2021 |
Keywords
- SPECT
- carbonic anhydrase IX
- clear cell renal cell carcinoma
- clinical trials
- molecular imaging
ASJC Scopus subject areas
- Analytical Chemistry
- Biochemistry
- Radiology Nuclear Medicine and imaging
- Drug Discovery
- Spectroscopy
- Organic Chemistry