# Multifunctional immunoPET tracers for pancreatic and prostate cancer

> **NIH NIH R01** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2020 · $358,858

## Abstract

PROJECT SUMMARY
Prostate and pancreatic cancers are among the most common and difficult to treat cancers. Major dilemmas in
the management of prostate cancer include the difficulty of discriminating between aggressive and indolent forms
of the disease and the need for improved treatment of high-risk and castrate resistant metastatic disease. In the
case of pancreatic cancer, the major problems are late diagnosis and high lethality. One major barrier to progress
and an unmet need in both diseases is the relative absence of effective molecular imaging tracers/tools that can
be used at the whole-body or intraoperative level, to guide patient management. Antibodies can provide highly
specific probes for molecular targets, and can be engineered to optimize their utility as imaging agents for clinical
use. During the previous project period, novel immunoPET imaging agents have been developed based on
engineered antibody fragments directed towards Prostate Stem Cell Antigen (PSCA), a cell surface biomarker
expressed by a majority of prostate and pancreatic cancers which is also a promising therapeutic target. Two
fragment formats, cys-diabody and cys-minibody, which enable site-specific conjugation and labeling, have been
produced with the goal of providing multifunctional fragments that can be radiolabeled with positron-emitting
radionuclides 124I, 89Zr, or 18F, and/or conjugation with fluorescent labels for optical imaging. In the proposed
work, fluorescently labeled PSCA cys-diabodies and cys-minibodies will be developed as intraoperative
molecular imaging probes and their utility assessed in preclinical models. Dually labeled probes (PET/optical)
will also be produced such that the same probe can be used for whole-body imaging followed by intraoperative
visualization of local/regional spread. Finally, based on promising biodistribution and imaging studies of
minibodies in patients, the therapeutic potential of radiolabeled anti-PSCA cys-minibodies will be explored,
comparing non-residualizing (131I) and residualizing (177Lu) therapeutic radionuclides. Full biodistributions will be
performed for dose estimations (mouse and human dosimetry), followed by radioimmunotherapy studies in
preclinical models. Furthermore, the efficiacy of PSCA-targeted radioimmunotherapy in combination with
androgen ablation or PARP inhibition will be evaluated. These fully humanized immunoPET probes can be
readily translated to the clinic to address pressing questions in clinical management, including staging of newly
diagnosed, recurrent and metastatic prostate and pancreatic cancers; improved selection and classification of
patients for PSCA-targeted therapy; and monitoring disease response to therapy, and ultimately could serve as
an efficacious delivery vehicle for tumor-targeted radiotherapy.

## Key facts

- **NIH application ID:** 9983602
- **Project number:** 5R01CA174294-08
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** ROBERT E REITER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $358,858
- **Award type:** 5
- **Project period:** 2013-04-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983602

## Citation

> US National Institutes of Health, RePORTER application 9983602, Multifunctional immunoPET tracers for pancreatic and prostate cancer (5R01CA174294-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9983602. Licensed CC0.

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