Abstract
Abstract 7188: Theranostics targeting the calcitonin gene-related peptide receptor (CGRPR) demonstrate efficacy in a preclinical mouse model of human cancer
Cancer research (Chicago, Ill.), Vol.86(7_Supplement), pp.7188-7188
04/03/2026
DOI: 10.1158/1538-7445.AM2026-7188
Abstract
Introduction:
Recent literature demonstrates that the CGRPR, and its primary ligand, calcitonin gene-related peptide (CGRP) are implicated in 9 of the 14 hallmarks of cancer and contribute to the development of multiple primary cancers. Here, we developed a theranostic strategy for the SPECT imaging and targeted radiotherapy of CGRPR-positive tumors.
Methods:
The CGRPR-specific bioconjugate DOTA-Bn-NCS-FV-Tic-TDVGPFAF (ACP) was radiolabelled with 111In (SPECT: t1/2 = 2.8 d; Ee-max = 0.245 MeV) or 177Lu (β - emitter: t1/2 = 6.7d; E β-max = 0.497 MeV). Biodistribution studies in CGRPR+ HTB-10 tumor-bearing mice were conducted using [111In]In-ACP and radioactivity in tissue was quantified against a known radioactivity standard. Therapy studies with [177Lu]Lu-ACP in the same tumor bearing model were also completed. As animals reached clinical endpoints, the animals were euthanized and processed for histology. QuPath software was used to quantify immunohistochemistry images, while survival and statistical analysis was accomplished using GraphPad Prism v.10.2.
Results:
The acute biodistribution of [111In]In-ACP revealed rapid excretion from blood, liver, kidney and bone suggesting effective clearance that may lead to acceptable dosimetry in dose-limiting organs such as the kidney and bone marrow. A tumor-to-muscle ratio of 39 at 4 h p.i., which was reduced to 12 with peptide blockade suggests that the radiopharmaceutical interacts with the CGRPR through a receptor mediated mechanism. Radiotherapy studies revealed that CGRPR+ HTB-10 tumor bearing mice injected with [177Lu]Lu-ACP experienced a survival benefit when compared to animals receiving control treatments (p = 0.036). When analysed histologically, tumor sections from animals receiving the radiotherapy exhibited decreased Ki-67 staining (proliferation marker) but higher caspase-3 (apoptosis marker) staining when compared to tumor sections of untreated animals.
Conclusion:
Although the CGRPR/CGRP axis is implicated in cancer development, no theranostic strategies exist currently that target this receptor for imaging and therapy. Available data with [111In]In-ACP revealed effective tumor targeting and rapid clearance from normal tissues, while radiotherapy studies with [177Lu]Lu-ACP demonstrated effective tumor growth control. These results suggest targeting the CGRPR/CGRP axis warrants further exploration as a promising new strategy for the imaging and therapy of cancer.
Details
- Title: Subtitle
- Abstract 7188: Theranostics targeting the calcitonin gene-related peptide receptor (CGRPR) demonstrate efficacy in a preclinical mouse model of human cancer
- Creators
- Prabhakar Eeka - University of IowaDarpan N. Pandya - University of IowaAndrew F. Russo - University of IowaYusuke Shiozawa - Wake Forest UniversityThaddeus J. Wadas - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Cancer research (Chicago, Ill.), Vol.86(7_Supplement), pp.7188-7188
- DOI
- 10.1158/1538-7445.AM2026-7188
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Publisher
- American Association for Cancer Research
- Language
- English
- Date published
- 04/03/2026
- Academic Unit
- Neurology; Radiology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Radiation Oncology; Craniofacial Anomalies Research Center
- Record Identifier
- 9985152089902771
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