Biodistribution and Radiation Dosimetric Analysis of [68Ga]Ga-RM2: A Potent GRPR Antagonist in Prostate Carcinoma Patients

Haendeler, Matthias; Khawar, Ambreen; Ahmadzadehfar, Hojjat; Kürpig, Stefan; Meisenheimer, Michael; Essler, Markus; Gaertner, Florian; Bundschuh, Ralph A.

doi:10.3390/radiation1010004

Cited by 5 publications

(3 citation statements)

References 25 publications

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“…Additionally, it has been shown that also metastases of hormone-refractory prostate carcinomas were GRPr-positive [11]. This is in line with clinical results on bombesin-based PET/CT showing promising results in patients with advanced disease in the sense of biochemical recurrence [56,57,58,59,111,112] and mCRPC patients see ▶ Fig. 1.…”

Section: Discussion On Application Of Bombesin-derivatives In Prostat...mentioning

confidence: 94%

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GRPr Theranostics: Current Status of Imaging and Therapy using GRPr Targeting Radiopharmaceuticals

et al. 2022

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Addressing molecular targets, that are overexpressed by various tumor entities, using radiolabeled molecules for a combined diagnostic and therapeutic (theranostic) approach is of increasing interest in oncology. The gastrin-releasing peptide receptor (GRPr), which is part of the bombesin family, has shown to be overexpressed in a variety of tumors, therefore, serving as a promising target for those theranostic applications. A large amount of differently radiolabeled bombesin derivatives addressing the GRPr have been evaluated in the preclinical as well as clinical setting showing fast blood clearance and urinary excretion with selective GRPr-binding. Most of the available studies on GRPr-targeted imaging and therapy have evaluated the theranostic approach in prostate and breast cancer applying bombesin derivatives tagged with the predominantly used theranostic pair of 68Ga/177Lu which is the focus of this review.

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Section: Discussion On Application Of Bombesin-derivatives In Prostat...mentioning

confidence: 94%

“…Organ absorbed doses of [ 68 Ga]Ga-RM2 were lower than [ 68 Ga]Ga-PSMA-11, excepted for urinary bladder, pancreas and stomach wall, and comparable to other GRPr antagonists. The authors concluded that [ 68 Ga]Ga-RM2 is a safe and useful diagnostic agent for PC patients [112].…”

Section: Rm1 -Rm2mentioning

confidence: 99%

GRPr Theranostics: Current Status of Imaging and Therapy using GRPr Targeting Radiopharmaceuticals

et al. 2022

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“…To our knowledge, there is no head-to-head comparison of radiolabeled NeoB and RM2 in patients and comparing results of separately performed studies is challenging due to methodological differences and differences in the patient’s characteristics. Despite this, we attempted to compare dosimetry calculations reported in two clinical studies using [ 68 Ga]Ga-NeoB and [ 68 Ga]Ga-RM2 [ 38 , 39 ]. In this comparison, the reported dose delivered to the pancreas, liver, and bladder was higher with radiolabeled NeoB vs. radiolabeled RM2.…”

Section: Discussionmentioning

confidence: 99%

Side-by-side comparison of the two widely studied GRPR radiotracers, radiolabeled NeoB and RM2, in a preclinical setting

Damiana,

Paraïso,

de Ridder

et al. 2023

Eur J Nucl Med Mol Imaging

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Introduction NeoB and RM2 are the most investigated gastrin-releasing peptide receptor (GRPR)–targeting radiotracers in preclinical and clinical studies. Therefore, an extensive side-by-side comparison of the two radiotracers is valuable to demonstrate whether one has advantages over the other. Accordingly, this study aims to compare the in vitro and in vivo characteristics of radiolabeled NeoB and RM2 to guide future clinical studies. Method The stability of the radiolabeled GRPR analogs was determined in phosphate buffered saline (PBS), and commercially available mouse and human serum. Target affinity was determined by incubating human prostate cancer PC-3 cells with [177Lu]Lu-NeoB or [177Lu]Lu-RM2, + / − increasing concentrations of unlabeled NeoB, RM2, or Tyr4-bombesin (BBN). To determine uptake and specificity cells were incubated with [177Lu]Lu-NeoB or [177Lu]Lu-RM2 + / − Tyr4-BBN. Moreover, in vivo studies were performed to determine biodistribution and pharmacokinetics. Finally, radiotracer binding to various GRPR-expressing human cancer tissues was investigated. Results Both radiotracers demonstrated high stability in PBS and human serum, but stability in mouse serum decreased substantially over time. Moreover, both radiotracers demonstrated high GRPR affinity and specificity, but a higher uptake of [177Lu]Lu-NeoB was observed in in vitro studies. In vivo, no difference in tumor uptake was seen. The most prominent difference in uptake in physiological organs was observed in the GRPR-expressing pancreas; [177Lu]Lu-RM2 had less pancreatic uptake and a shorter pancreatic half-life than [177Lu]Lu-NeoB. Furthermore, [177Lu]Lu-RM2 presented with a lower tumor-to-kidney ratio, while the tumor-to-blood ratio was lower for [177Lu]Lu-NeoB. The autoradiography studies revealed higher binding of radiolabeled NeoB to all human tumor tissues. Conclusion Based on these findings, we conclude that the in vivo tumor-targeting capability of radiolabeled NeoB and RM2 is similar. Additional studies are needed to determine whether the differences observed in physiological organ uptakes, i.e., the pancreas, kidneys, and blood, result in relevant differences in organ absorbed doses when the radiotracers are applied for therapeutic purposes.

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PET imaging of prostate cancer

Ong

Hofman

2022

Nuclear Medicine and Molecular Imaging

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Biodistribution and Radiation Dosimetric Analysis of [68Ga]Ga-RM2: A Potent GRPR Antagonist in Prostate Carcinoma Patients

Cited by 5 publications

References 25 publications

GRPr Theranostics: Current Status of Imaging and Therapy using GRPr Targeting Radiopharmaceuticals

GRPr Theranostics: Current Status of Imaging and Therapy using GRPr Targeting Radiopharmaceuticals

Side-by-side comparison of the two widely studied GRPR radiotracers, radiolabeled NeoB and RM2, in a preclinical setting

PET imaging of prostate cancer

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