Indication for Different Mechanisms of Kidney Uptake of Radiolabeled Peptides

Gotthardt, Martin; Eerd-Vismale, Julliëtte van; Oyen, Wim J.G.; Jong, Marion de; Zhang, Hanwen; Rolleman, Edgar J.; Maecke, Helmut R.; Béhé, Martin; Boerman, Otto C.

doi:10.2967/jnumed.106.036020

Cited by 150 publications

(186 citation statements)

References 18 publications

Supporting

Mentioning

164

Contrasting

Unclassified

Order By: Relevance

“…Some of these approaches are clinically validated and have become part of the standard protocols in peptide receptor radionuclide therapy (33,34). However, this principle is not applicable to all compounds and efficiency can vary greatly between different types of radiolabeled compounds (35). Here we show that this principle does apply for 99m Tc-7C12 nanobody.…”

Section: Discussionmentioning

confidence: 88%

Localization, mechanism and reduction of renal retention of technetium‐99m labeled epidermal growth factor receptor‐specific nanobody in mice

Gainkam

Caveliers

Devoogdt

et al. 2010

Contrast Media & Molecular

119

View full text Add to dashboard Cite

Background: Nanobodies are single-domain antigen binding fragments derived from functional heavy-chain antibodies elicited in Camelidae. They are powerful probes for radioimmunoimaging, but their renal uptake is relatively high. In this study we have evaluated the role of megalin on the renal uptake of anti-EGFR 99m Tc-7C12 nanobody and the potency of gelofusine and/or lysine to reduce renal uptake of 99m Tc-7C12. Methods: First we compared the renal uptake of 99m Tc-7C12 in megalin-deficient and megalin-wild-type mice using pinhole SPECT/microCT and ex vivo analysis. The effect of gelofusine and lysine administration on renal accumulation of 99m Tc-7C12 was analyzed in CD-1 mice divided into lysine preload at 30 min before tracer injection (LysPreload), LysPreload R gelofusine coadministration (LysPreload R GeloCoad), lysine coadministration (LysCoad), gelofusine coadministration (GeloCoad) and LysCoad R GeloCoad. The combined effect of gelofusine and lysine on tumor uptake was tested in mice xenografts. Results: Renal uptake of 99m Tc-7C12 was 44.22 W 3.46% lower in megalin-deficient compared with megalinwild-type mice. In CD-1 mice, lysine preload had no effect on the renal retention whereas coinjection of lysine or gelofusine with the tracer resulted in 25.12 W 2.99 and 36.22 W 3.07% reduction, respectively. The combined effect of gelofusine and lysine was the most effective, namely a reduction of renal retention of 45.24 W 2.09%. Gelofusine and lysine coadministration improved tumor uptake. Conclusion: Megalin contributes to the renal accumulation of 99m Tc-7C12. Gelofusine and lysine coinjection with the tracer reduces the renal uptake while tumor uptake is improved. Although this methodology allows for optimization of imaging protocol using nanobodies, further improvements are needed before using these molecules for radionuclide therapy.

show abstract

Section: Discussionmentioning

confidence: 88%

Localization, mechanism and reduction of renal retention of technetium‐99m labeled epidermal growth factor receptor‐specific nanobody in mice

Gainkam

Caveliers

Devoogdt

et al. 2010

Contrast Media & Molecular

119

View full text Add to dashboard Cite

show abstract

“…Because the truncated peptide GIP(1-30) activates the GIP receptor as efficiently as the fulllength peptide GIP(1-42) (25), the GIP(1-30) was chosen as the peptide motif of our study. The peptide was functionalized with the chelator DOTA via 6-Ahx coupled to the side chains of Lys 16 and Lys 30 , respectively, to obtain EG1, EG2, and EG4. In EG4, the Met 14 was substituted with Nle, as a widely used strategy for stabilizing peptides against oxidative damage and allowing easier handling.…”

Section: Discussionmentioning

confidence: 99%

“…Uptake of radiolabeled peptides in kidneys is a major problem because of the nephrotoxicity caused by the accumulated activity. This problem is even more pronounced if therapeutic applications are planned (30). The rationale for using Gelofusine as a reuptake blocking agent relies on the fact that the metallated DOTA-conjugated peptides contain 3 Asp, 1 Glu, and 1 Lys, having 3 negative charges at physiologic pH, Gelofusine is a succinylated gelatin with a net negative surface charge.…”

mentioning

confidence: 99%

The Glucose-Dependent Insulinotropic Polypeptide Receptor: A Novel Target for Neuroendocrine Tumor Imaging—First Preclinical Studies

Gourni

Waser

Clerc³

et al. 2014

J Nucl Med

View full text Add to dashboard Cite

A new family of peptide receptors, the incretin receptor family, overexpressed on many neuroendocrine tumors (NETs) is of great importance because it may enable the in vivo peptide-based receptor targeting of a category of NETs that does not express the somatostatin receptor. Impressive in vivo diagnostic data were published for glucagonlike peptide 1 receptor-targeting radiopeptides. Recently, promising in vitro data have appeared for the second member of the incretin family, the glucose-dependent insulinotropic polypeptide (GIP) receptor. This prompted us to develop and evaluate a new class of radioligands with the potential to be used for the in vivo targeting of GIP receptor-positive tumors. Methods: GIP(1-42) was modified C-terminally, and the truncated peptides showed high affinity toward GIP receptor for the GIP conjugates. Specific in vitro internalization was found, and almost the entire cellassociated activity was internalized (.90% of the cell-bound activity), supporting the agonist potency of the 111 In-EG4 and 68 Ga-EG4 were shown to specifically target INR1G9-hGIPr xenografts, with tumor uptake of 10.4% ± 2.2% and 17.0% ± 4.4% injected activity/g, 1 h after injection, respectively. Kidneys showed the highest uptake, which could be reduced by approximately 40%-50% with a modified-fluid-gelatin plasma substitute or an inhibitor of the serine protease dipeptidyl peptidase 4. The PET images clearly visualized the tumor. Conclusion: The evaluation of EG4 as a proof-ofprinciple radioligand indicated the feasibility of imaging GIP receptorpositive tumors. These results prompt us to continue the development of this family of radioligands for imaging of a broad spectrum of NETs.

show abstract

“…For renal uptake reduction studies, 80 mg (3-15 kD) of L-polyglutamic acid (PGA; Sigma-Aldrich) per milliliter or 40 mg of Gelofusine (Braun) per milliliter were dissolved in saline as described previously (28). Rip1Tag2 mice were injected intravenously with 100 mL of one solution or 200 mL of both solutions just before intravenous administration of 10 pmol of Values and SD are result of 2 independent experiments (triplicates in each experiment) and are expressed as specific internalization (% added radioactivity/10 6 cells 6 SD).…”

Section: Renal Uptake Reduction Studiesmentioning

confidence: 99%

Exendin-4–Based Radiopharmaceuticals for Glucagonlike Peptide-1 Receptor PET/CT and SPECT/CT

et al. 2010

View full text Add to dashboard Cite

Tc/EDDA)NH 2 ]-exendin-4 did not result in inferior tumor-to-organ ratios or reduced image quality. All radiopeptides tested showed a high tumor-to-background ratio, resulting in the visualization of small tumors (maximum diameter between 1.0 and 3.2 mm) by SPECT and PET. The only exception was the kidneys, which also showed high uptake. This uptake could be reduced by 49%278% using poly-glutamic acid, Gelofusine, or a combination of the 2. The estimated effective radiation dose was 3.7 mSv/MBq for [Lys 40

show abstract

Indication for Different Mechanisms of Kidney Uptake of Radiolabeled Peptides

Cited by 150 publications

References 18 publications

Localization, mechanism and reduction of renal retention of technetium‐99m labeled epidermal growth factor receptor‐specific nanobody in mice

Localization, mechanism and reduction of renal retention of technetium‐99m labeled epidermal growth factor receptor‐specific nanobody in mice

The Glucose-Dependent Insulinotropic Polypeptide Receptor: A Novel Target for Neuroendocrine Tumor Imaging—First Preclinical Studies

Exendin-4–Based Radiopharmaceuticals for Glucagonlike Peptide-1 Receptor PET/CT and SPECT/CT

Contact Info

Product

Resources

About