Optimizing FAPI homodimers for theranostic applications: The impact of the linker design in DOTAGA.Glu 2…

Animal / preclinicalEuropean journal of nuclear medicine and molecular imaging· Jul 2026

Optimizing FAPI homodimers for theranostic applications: The impact of the linker design in DOTAGA.Glu 2 .(FAPI) 2 and DOTAGA.PEG 2 .Glu.(FAPI) 2 .

Naveen Kumar, Adrianna Bilinska, Elena Menéndez … Eleni Gourni

TheranosticsAnimal / preclinicalQ1IF 5.8

DOTAGA.Glu2.(FAPI)2 gave 2-fold higher tumor drug exposure than the PEG-linked analog

Optimizing FAPI homodimers for theranostic applications: The impact of the linker design in DOTAGA.Glu 2 .(FAPI) 2 and DOTAGA.PEG 2 .Glu.(FAPI) 2 .

Naveen Kumar … Eleni Gourni

European journal of nuclear medicine and molecular imaging · Jul 2026 · Q1 in Radiology

Purpose

This study evaluated the imaging performance, tumor retention, and therapeutic potential of two new FAPI homodimers, DOTAGA.

Methods

DOTAGA.

2-fold

Results

2-fold

tumor drug levels ran higher with the Glu2 linker than the PEG linker

More results

All radioligands showed > 99% radiochemical purity, high FAP affinity (K d : 0.9-1.5 nM), hydrophilic profiles (LogD octanol/PBS ≤-3), and low protein binding (< 10%).

They exhibited high internalization and low externalization (~ 20% for [ 177 Lu]Lu-DOTAGA.

More results

The 68 Ga-labeled radiotracers displayed sustained tumor uptake up to 3 h p.i.

For the 177 Lu-labeled analogues the initial uptake was comparable (~ 15%I.

“

Conclusion

DOTAGA. Glu 2 .(FAPI) 2 demonstrates superior tumor retention, favorable pharmacokinetics, and enhanced therapeutic efficacy, supporting its potential for clinical translation.

Optimizing FAPI homodimers for theranostic applications: The impact of the linker design in DOTAGA.Glu 2 .(FAPI) 2 and DOTAGA.PEG 2 .Glu.(FAPI) 2 .

Optimizing FAPI homodimers for theranostic applications: The impact of the linker design in DOTAGA.Glu 2 .(FAPI) 2 and DOTAGA.PEG 2 .Glu.(FAPI) 2 .

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