Table 5.

Strategies to lower kidney uptake of exendin‐4–based tracers and their efficacy as described in various studies

Strategy	Outcome
Cleavable linker	• No significant change in kidney retention in comparison with [111In]In‐Ex4NOD40. It was assumed that the peptides were not cleaved before reabsorption in vivo.80
Inhibition of neutral endopeptidases	• Polygelines Haemaccel and gelofusine both increased urinary secretion of protein β2‐microglobulin, most likely explained by competitive inhibition of tubular protein reabsorption.81
	• Gelofusine and poly‐glutamic acid (PGA) reduced kidney uptake by 18.7% and 29.4%, respectively. Gelofusine and PGA combined decreased kidney uptake by 47.9%.79
	• Gelofusine, albumin fragments, and lysine decreased renal uptake by 52%, 25%, and 15%, respectively.82
	• Albumin‐derived peptide lowered renal uptake by 26% while gelofusine led to a reduction of 16%.84
Incorporation of highly lipophilic groups	• Kidney uptake was considerably lower compared with radiometal‐labeled compounds and ranged from 30 to 50 %ID/g.34