In vivo pH imaging with (99m)Tc-pHLIP

Area of Science:

• Molecular imaging
• Biomedical engineering
• Radiochemistry

Background:

• A novel molecular imaging agent, the pH (low) insertion peptide (pHLIP), targets tissues with low extracellular pH.
• pHLIP exhibits pH-dependent folding and membrane insertion in vitro.
• Previous studies demonstrated in vivo tumor targeting using fluorescence and PET labels.

Purpose of the Study:

• To evaluate the feasibility of pHLIP labeled with SPECT, specifically 99mTc-AH114567.
• To assess the preclinical efficacy and imageability of 99mTc-AH114567 for targeting acidic solid tumors.

Main Methods:

• Lewis lung carcinoma, prostate lymph node carcinoma, and prostate adenocarcinoma xenografts were grown in mice.
• Tumor characterization included angiogenesis marker 99mTc-NC100692 and extracellular pH measurement via 31P-MRS.
• Biodistribution and CT/SPECT imaging were performed; oral bicarbonate administration served as a control.

Main Results:

• 99mTc-AH114567 was synthesized robustly with good radiolabeling and formulation.
• The tracer maintained pH-dependent membrane insertion and tumor targeting capabilities, similar to previous pHLIP agents.
• SPECT imaging provided adequate image quality and contrast, despite SPECT's inherent sensitivity limitations.

Conclusions:

• 99mTc-AH114567 shows promise as a SPECT imaging agent for acidic tumors.
• The tracer demonstrates comparable pharmacokinetics and efficacy to optical and PET-labeled pHLIP agents.
• Further optimization is needed to enhance background signal reduction for clinical translation.