# Investigating the Theranostic Potential of Elementally Matched [43Sc]Sc-PSMA-617 and [47Sc]Sc-PSMA-617

## TL;DR

This study shows that scandium-based radiopharmaceuticals can be used together for both diagnosing and treating prostate cancer, with diagnostic results predicting treatment outcomes.

## Contribution

Demonstrates the theranostic potential of elementally matched 43Sc and 47Sc radiopharmaceuticals for prostate cancer.

## Key findings

- 43Sc and 47Sc were incorporated into PSMA-617 with >99% radiochemical yield.
- PET imaging with 43Sc correlated strongly with therapeutic response from 47Sc in tumor models.
- 47Sc delayed tumor growth and increased survival in xenograft models.

## Abstract

The theranostic approach,
which employs diagnostic radiopharmaceuticals
to select patients who would benefit from targeted radiotherapy agents,
has become an invaluable strategy for effective medical care. Scandium
radionuclides offer the advantage of forming elementally matched and
chemically identical diagnostic and therapeutic compounds, making
them ideal candidates for this strategy. PSMA-617 is an established
prostate-specific membrane antigen targeting agent and can be used
as a proof of concept to investigate 43Sc, the diagnostic
nuclide, and 47Sc, the therapeutic nuclide, as a theranostic
pair. Methods: Cellular uptake, competitive binding assays, and internalization
studies were carried out using LNCaP or PC-3 cell lines. [43Sc]­Sc-PSMA-617 was used in PET imaging studies in LNCaP or PC-3 tumor
models, with time points ranging from 1–9 h. LNCaP tumor-bearing
mice injected with [47Sc]­Sc-PSMA-617 were imaged using
SPECT up to 48 h. A longitudinal study was carried out using LNCaP
tumor-bearing mice imaged with [43Sc]­Sc-PSMA-617 prior
to receiving a therapeutic dose of [47Sc]­Sc-PSMA-617. Results: 43Sc and 47Sc were incorporated into PSMA-617 at
radiochemical yields of >99%. Cellular uptake studies demonstrated
high uptake and specificity to PSMA receptors for [47Sc]­Sc-PSMA-617. In vivo PET studies showed specificity of [43Sc]­Sc-PSMA-617 while SPECT studies demonstrated tumor retention of
[47Sc]­Sc-PSMA-617 up to 48 h. [47Sc]­Sc-PSMA-617
demonstrated therapeutic efficacy by delaying tumor growth and increasing
survival rates from a single administered dose in xenograft models.
More importantly, the PET results from [43Sc]­Sc-PSMA-617
PET were highly correlated with the therapeutic response from [47Sc]­Sc-PSMA-617, showing that 43Sc PET data can
predict therapeutic outcomes in individual animals from 47Sc agents, even in animals sharing a genetic background and implanted
with tumors from the same cell line. Conclusions: Two chemically identical,
PSMA-targeting radioscandium pharmaceuticals demonstrated in vivo stability, specificity and retention in PSMA+ tumor
models. A theranostic study showed that a higher 43Sc PET
SUVmean was strongly correlated to therapeutic response
from the 47Sc agent, demonstrating that 43Sc
and 47Sc can be used as an elementally matched theranostic
pair.