The DB4 (N4-Pro-Gln-Arg-Tyr-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Nle-NH2, N4 = 6-(carboxy)-1,4,8,11-tetraazaundecane) and SG4 (DOTA-DGlu-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH2, DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) peptide conjugates (Figure 1 ) were provided by PiChem (Graz, Austria). [Tyr4]BBN (Pyr-Gln-Arg-Tyr-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2) was purchased from Bachem (Bubendorf, Switzerland). The neprilysin (NEP)-inhibitor sacubitrilat (LBQ657, (2R,4S)-4-(3-carboxypropanoylamino)-2-methyl-5-(4-phenylphenyl)-pentanoic acid) was obtained from BIOMOL GmbH (Hamburg, Germany), while Entresto pills (200 mg corresponding to 24 mg/26 mg sacubitril/valsartan per pill) containing the prodrug sacubitril (AHU377, 4-[[(2S,4R)-5-ethoxy-4-methyl-5-oxo-1-(4-phenylphenyl)pentan-2-yl]amino]-4oxobutanoic acid) (Figure 1 ) (Novartis, Basel, Switzerland) were purchased from a local pharmacy. For animal treatment (vide infra), whole pills were ground to a fine powder in a mortar, divided and suspended in tab water to individual 12 mg/200 mL doses of pill per animal [32 (link)].
Technetium-99m in the form of [99mTc]NaTcO4 was collected by elution of a [99Mo]Mo/[99mTc]Tc generator (Ultra-Technekow™ V4 Generator, Curium Pharma, Petten, The Netherlands). Indium-111 as an [111In]InCl3 solution was purchased from Curium Pharma (Petten, The Netherlands).
Technetium-99m in the form of [99mTc]NaTcO4 was collected by elution of a [99Mo]Mo/[99mTc]Tc generator (Ultra-Technekow™ V4 Generator, Curium Pharma, Petten, The Netherlands). Indium-111 as an [111In]InCl3 solution was purchased from Curium Pharma (Petten, The Netherlands).