Abstract

We evaluated the ability of monosodium glutamate (MSG) to reduce salivary and kidney uptake of a prostate-specific membrane antigen (PSMA) radioligand without affecting tumor uptake. Methods: LNCaP tumor–bearing mice were intraperitoneally injected with MSG (657, 329, or 164 mg/kg) or phosphate-buffered saline (PBS). Fifteen minutes later, the mice were intravenously administered 68Ga-PSMA-11. PET/CT imaging and biodistribution studies were performed 1 h after administration. Results: Tumor uptake (percentage injected dose per gram [%ID]) was not statistically different between groups, at 8.42 ± 1.40 %ID in the 657 mg/kg group, 7.19 ± 0.86 %ID in the 329 mg/kg group, 8.20 ± 2.44 %ID in the 164 mg/kg group, and 8.67 ± 1.97 %ID in the PBS group. Kidney uptake was significantly lower in the 657 mg/kg group (85.8 ± 24.2 %ID) than in the 329 mg/kg (159 ± 26.2 %ID), 164 mg/kg (211 ± 27.4 %ID), and PBS groups (182 ± 33.5 %ID) (P < 0.001). Salivary gland uptake was lower in the 657 mg/kg (3.72 ± 2.12 %ID) and 329 mg/kg (5.74 ± 0.62 %ID) groups than in the PBS group (10.04 ± 2.52 %ID) (P < 0.01). Conclusion: MSG decreased salivary and kidney uptake of 68Ga-PSMA-11 in a dose-dependent manner, whereas tumor uptake was unaffected.

Highlights

  • Prostate-specific membrane antigen (PSMA) is an excellent prostate cancer target for theranostic applications

  • We investigated monosodium glutamate (MSG) for reducing uptake of 68Ga-PSMA-11 in the salivary glands and kidneys in LNCaP tumor–bearing mice

  • PSMA is expressed in the salivary glands and kidneys, part of PSMA-ligand uptake in salivary glands may be due to off-target binding, as uptake is not observed in human studies with the radiolabeled J591 monoclonal antibody [12,13,14]

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Summary

Introduction

Prostate-specific membrane antigen (PSMA) is an excellent prostate cancer target for theranostic applications. The activity administered to patients is limited by toxicity to normal organs; high uptake is observed in the lacrimal glands, parotid glands, submandibular glands, and renal cortex [4]. Botulinum toxin was administered to the parotid gland of a patient and significantly decreased PSMA-ligand uptake [9]. This procedure is promising, it is invasive and costly and may affect salivary gland function for weeks. PSMA is expressed in the salivary glands and kidneys, part of PSMA-ligand uptake in salivary glands may be due to off-target binding, as uptake is not observed in human studies with the radiolabeled J591 monoclonal antibody [12,13,14]. Because many PSMA ligands integrate glutamate for binding to PSMA, we hypothesized that MSG could reduce nonspecific accumulation in noncancerous tissues

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Conclusion

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