[99mTc]HYNIC-RGD for imaging integrin alphavbeta3 expression.

Area of Science:

• Radiochemistry
• Molecular Imaging
• Oncology

Background:

• Increasing interest in Arg-Gly-Asp (RGD) peptides for alpha(v)beta(3) integrin targeting in angiogenesis imaging.
• [(18)F]Galacto-RGD is established for PET imaging; a SPECT equivalent is needed.

Purpose of the Study:

• To characterize a novel (99m)Tc-labeled RGD peptide derivative, [99mTc]EDDA/HYNIC-RGD, for SPECT imaging of alpha(v)beta(3) integrins.
• To evaluate its preclinical efficacy in vitro and in vivo.

Main Methods:

• Synthesis and (99m)Tc labeling of HYNIC-RGD peptide using various coligands.
• In vitro characterization: lipophilicity, protein binding, stability, and cell uptake assays.
• In vivo biodistribution studies in mice bearing tumors with varying alpha(v)beta(3) integrin expression.

Main Results:

• [99mTc]EDDA/HYNIC-RGD achieved high specific activity, exhibited low lipophilicity (log P = -3.56), and demonstrated high in vitro stability.
• Specific and rapid cell uptake was observed in alpha(v)beta(3)-positive M21 cells.
• In vivo studies showed rapid renal excretion, low non-specific uptake, and significant tumor uptake in alpha(v)beta(3)-positive tumors (2.73% ID/g vs. 0.85% ID/g).
• Small cell lung tumors were visualized using gamma camera imaging.

Conclusions:

• [99mTc]EDDA/HYNIC-RGD is a promising SPECT imaging agent for alpha(v)beta(3) integrins.
• It possesses favorable stability, pharmacokinetics, and specific tumor targeting capabilities.
• Its performance is comparable to [(18)F]Galacto-RGD, suggesting potential clinical translation for angiogenesis imaging.