Diagnosis of Prostate Cancer with a Neurotensin-Bombesin Radioligand Combination-First Preclinical Results

Area of Science:

• Nuclear Medicine
• Oncology
• Radiopharmaceutical Chemistry

Background:

• Radiotheranostics leverage target overexpression on cancer cells for targeted delivery of diagnostic/therapeutic agents.
• Exploiting multiple targets simultaneously can enhance diagnostic sensitivity and therapeutic efficacy.
• This study investigates a novel dual-targeting approach for prostate cancer using two technetium-99m labeled tracers.

Purpose of the Study:

• To evaluate the combined efficacy of [^99mTc]Tc-DT11 (NTS₁R-specific) and [^99mTc]Tc-DB7 (GRPR-specific) in prostate cancer models.
• To assess the impact of Entresto® (sacubitrilat) on the tumor uptake of these radiotracers.

Main Methods:

• Comparison of [^99mTc]Tc-DT11 alone versus a mixture of [^99mTc]Tc-DT11 and [^99mTc]Tc-DB7 in PC-3 prostate cancer cells and xenografts.
• In vivo studies in mice to quantify tumor uptake at 4 hours post-injection.
• Evaluation of radiotracer stabilization using Entresto®.

Main Results:

• The [^99mTc]Tc-DT11 + [^99mTc]Tc-DB7 mixture demonstrated significantly higher PC-3 cell binding compared to [^99mTc]Tc-DT11 alone.
• Tumor uptake of the dual-tracer mixture was superior (7.70 ± 0.89%IA/g) to single-tracer uptake (4.23 ± 0.58%IA/g; p < 0.0001).
• Entresto® treatment further increased tumor uptake to 11.57 ± 1.92%IA/g (p < 0.0001).

Conclusions:

• Dual NTS₁R/GRPR targeting shows significant advantages in preclinical prostate cancer models.
• This combined approach offers enhanced tumor targeting and uptake compared to single-target strategies.
• Further investigation in diverse cancer models is warranted to explore the full potential of this theranostic strategy.