Optimizing theranostic dosimetry and kidney biomarkers for alpha-emitter radioligand therapy in neuroendocrine tumors
Active Project Grant Awarded Last action
- Award ID
- R01CA291827
- Recipient
-
Research Institute At Nationwide Children's Hospital UEI EYMJXLN2MFB4
- Awarding agency
-
National Cancer Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $2,930,402
Award facts
- Assistance listing
- 93.395 Cancer Treatment Research
- Completion date 47% complete
- Place of performance
- Columbus, OH 43205, USA
Award details come from USAspending.gov.
Description
- Abstract
- The somatostatin subtype 2 receptor (SSTR2) is expressed in 80-100% of nets. SSTR2 targeted alpha-emitter radioligand therapy (Α-RLT) is emerging as an exciting alternative to beta-emitter radiopharmaceuticals due to the higher linear energy transfer and dense ionization tracks that result in enhanced formation of double stranded DNA (DSDNA) damage with up to 80% tumor response rates in early clinical studies. However, preclinical studies show that Α-rlts can cause a dose dependent late nephrotoxicity characterized by late tubular injury, fibrosis, and inflammation. Building on recent breakthrough from our group we will test the overall hypothesis that [212PB]PB-VMT-Α-net (212PB-VMT) tumor responses can be maximized through a treatment scheme that incorporates biomarkers of tubular injury, dosimetry, dose fractionation, and a nephroprotective superoxide dismutase mimetic to mitigate nephrotoxicity. In aim 1, we will develop a detailed understanding of the role of superoxide dismutation in tubular DSDNA repair following [212PB]PB-VMT-Α-net treatment. In aim 2, we will identify [212PB]PB-VMT-Α-net dosing regimens to achieve maximal tumor responses and reduce nephrotoxicity using a superoxide dismutase mimetic. We will incorporate the following innovative methods: (1) a novel Α-RLT [203PB/212PB]PB-VMT-Α-net theranostic pair targeting SSTR2; (2) innovative SSTR2 expressing tumor models; (3) urine biomarkers for non-invasive detection of tubular injury; (4) DSDNA injury/repair tools to study mechanism of early subclinical tubular DSDNA damage following Α -RLT; and (5) a novel nephrotoxicity mitigation strategy based on superoxide scavenging that shows promising tumor response improvement to external beam radiation. If successful, we expect these findings and advances be transferable to a broad range of Α-rlts, not only for pancreatic nets and neuroblastoma, but also for prostate, breast, melanomas, and other difficult to treat cancers amenable to Α-RLT.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $1,703,256 | |
| Amendment | $0 | |
| Amendment | $599,573 | |
| Original award | $627,573 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| Viewpoint Molecular Targeting, Inc. | $71,196 | |
| The University Of Iowa | $152,948 |
Quick answers
Who received award R01CA291827?
R01CA291827 was awarded to Research Institute At Nationwide Children's Hospital by National Cancer Institute (National Institutes of Health) on July 1, 2024.
How much is award R01CA291827 worth?
$2,930,402 has been obligated on R01CA291827.
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