Evaluation of Tumor-Targeting Properties of an Antagonistic Bombesin Analogue RM26 Conjugated with a Non-Residualizing Radioiodine Label Comparison with a Radiometal-Labelled Counterpart

Abstract

Radiolabelled antagonistic bombesin analogues are successfully used for targeting of gastrin-releasing peptide receptors (GRPR) that are overexpressed in prostate cancer. Internalization of antagonistic bombesin analogues is slow. We hypothesized that the use of a non-residualizing radioiodine label might not affect the tumour uptake but would reduce the retention in normal organs, where radiopharmaceutical would be internalized. To test this hypothesis, tyrosine was conjugated via diethylene glycol linker to N-terminus of an antagonistic bombesin analogue RM26 to form Tyr-PEG2-RM26. [111In]In-DOTA-PEG2-RM26 was used as a control with a residualizing label. Tyr-PEG2-RM26 was labelled with 125I with 95% radiochemical purity and retained binding specificity to GRPR. The IC50 values for Tyr-PEG2-RM26 and DOTA-PEG2-RM26 were 1.7 ± 0.3 nM and 3.3 ± 0.5 nM, respectively. The cellular processing of [125I]I-Tyr-PEG2-RM26 by PC-3 cells showed unusually fast internalization. Biodistribution showed that uptake in pancreas and tumour was GRPR-specific for both radioconjugates. Blood clearance of [125I]I-Tyr-PEG2-RM26 was appreciably slower and activity accumulation in all organs was significantly higher than for [111In]In-DOTA-PEG2-RM26. Tumor uptake of [111In]In-DOTA-PEG2-RM26 was significantly higher than for [125I]I-Tyr-PEG2-RM26, resulting in higher tumour-to-organ ratio for [111In]In-DOTA-PEG2-RM26 at studied time points. Incorporation of amino acids with hydrophilic side-chains next to tyrosine might overcome the problems associated with the use of tyrosine as a prosthetic group for radioiodination.

Synthesis, 123I-Radiolabeling Optimization, and Initial Preclinical Evaluation of Novel Urea-Based PSMA Inhibitors with a Tributylstannyl Prosthetic Group in Their Structures

“…Lipophilicity of 123 I-PSMA was determined as the logarithm of the partition coefficient, log(D), of the 123 I-PSMA compound between n-octanol and water [44]. A volume of 500 µL of n-octanol was added to an Eppendorf tube containing the same volume of Milli-Q water.…”

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

“…Varasteh et al [22] clinical BC Zang et al [77,78] marily or secondary) PSMA-negative setting and serve as targets within a the theranostic approach in prostate cancer. Numerous radiolabeled bombesin-derivatives have been synthesized and evaluated in predominantly radiochemistry and preclinical studies including different radionuclides [92,93,105,106,107,108,109]. Due to the large amount on published data we focus on a selection of 68 Ga/ 177 Lu-labeled bombesin-derivatives.…”

Synthesis and Evaluation of [18F]FEtLos and [18F]AMBF3Los as Novel 18F-Labelled Losartan Derivatives for Molecular Imaging of Angiotensin II Type 1 Receptors

“…The cell binding assays were performed based on previous reports [66] with modifications. CHO-AT1R and CHO cells (2 × 10 5 ) were plated in a 6-well plate overnight and then incubated for one hour at 4 • C with 10 µCi (370 kBq) of [ 18 F]AMBF 3 Los per well, in presence or absence of the AT 1 R blocker (losartan potassium (100 µM/well) in PBS).…”