Phosphatidylserine (PS) is a phospholipid normally located in the inner leaflet of the cell membrane. PS is translocated from the inner to the outer leaflet of the plasma membrane during the early stages of apoptosis and in necrosis. In cell and animal studies, reversible PS externalisation to the outer membrane leaflet has been observed in viable cells. Hence, PS markers have been proposed as markers of both reversibly and irreversibly damaged cells. The purpose of this experimental study in pigs was to investigate the kinetics of the newly introduced PS marker technetium-99m-labelled lactadherin (99mTc-lactadherin) in comparison with the well-known PS tracer 99mTc-annexin V with special reference to the renal handling of the tracers. The effective dose for humans was estimated from the biodistribution in 24 mice.

Introduction. The aim of this study was to establish a radio synthesis of ^99mTc-HYNIC-lactadherin for in vivo studies and to perform biodistribution analysis studies in mice, comparing ^99mTc-HYNIC-lactadherin to ^99mTc-HYNIC-annexin V. Methods. The radiochemical purity of ^99mTc-HYNIC-lactadherin was optimized by varying the amount of SnCl₂ in the synthesis. Furthermore, the need for bovine serum albumin (BSA) as a stabilizing agent was evaluated by following the stability by radiochemical purity measurement with and without the addition of BSA. A total of 24 mice were assigned to groups of 15 and nine mice, respectively. The animals were sacrificed at different time points; 10 min, 60 min, and 180 min. Results. The synthesis of ^99mTc-HYNIC-lactadherin for in vivo studies has been optimized to give a stable product without addition of BSA and with a radiochemical purity of more than 95%. Approximately 60% of the injected dose of ^99mTc-HYNIC-lactadherin was found in the liver and 4–5% could be assigned to kidneys. In contrast, ^99mTc-HYNIC-annexin V distributes with around 13% and 45% of the injected dose in liver and kidneys, respectively. Over the experimental period (10–180 min) only small distributional changes were observed for both probes. Conclusion. In conclusion, the biodistribution of ^99mTc-HYNIC-lactadherin, a potential new tracer for in vivo quantification of apoptosis, was evaluated. The small renal uptake of ^99mTc-HYNIC-lactadherin makes it possible to image apoptosis in the kidneys, but the high liver clearance may be a disadvantage during myocardial perfusion.

The cyclotron production of gallium-68 via the ⁶⁸Zn(p,n)⁶⁸Ga nuclear reaction in liquid targets is gaining significant traction in clinics. This work describes (1) the synthesis of new arylamino phosphonates via the Kabachnik–Fields reaction, (2) their use for liquid–liquid extraction of ⁶⁸Ga from 1 M Zn(NO₃)₂/0.01 M HNO₃ in batch and continuous flow, and (3) the use of Raman spectroscopy as a process analytical technology (PAT) tool for in-line measurement of ⁶⁸Zn. The highest extraction efficiencies were obtained with the extractants functionalized with trifluoromethyl substituents and ethylene glycol ponytails, which were able to extract up to 90% of gallium-68 in batch and 80% in flow. Only ppm amounts of zinc were co-extracted. The extraction efficiency was a function of pKa and the aqueous solubility of the extractant and showed marked concentration, solvent, and temperature dependence. Raman spectroscopy was found to be a promising PAT tool for the continuous production of gallium-68.

Background: The purpose of the present study was to quantify renal cell injury after ischemia and reperfusion in a pig model using^99mTc-lactadherin as a marker of apoptosis and^99mTc-sestamibi as a marker of mitochondrial dysfunction.Methods: Thirty-four pigs were randomized into unilateral renal warm ischemia of 120 (WI₁₂₀) or 240 min (WI₂₄₀). The glomerular filtration rate (GFR) was calculated by renal clearance of⁵¹Cr-ethylenediaminetetraacetic acid, and apoptosis was quantified by immunohistochemical detection of caspase-3. After 240 min of reperfusion, intravenous^99mTc-lactadherin or^99mTc-sestamibi was injected simultaneously with¹⁵³Gd microspheres into the aorta.Ex-vivostatic planar images of the kidneys were acquired for determination of the differential renal function of tracer distribution using a gamma camera.Results: In WI₁₂₀, there was no significant difference in the uptake of microspheres in the ischemic and contralateral normal kidney indicating adequate perfusion (uptake in ischemic kidney relative to the sum of uptake in both kidneys; 46% ± 12% and 51% ± 5%). In WI₂₄₀, the uptake of microspheres was severely reduced in both groups (17% ± 11% and 27% ± 17%). GFR was severely reduced in the post ischemic kidney in both groups.In both groups, the uptake of lactadherin was reduced (41% ± 8%, 17% ± 13%) but not different from the uptake of¹⁵³Gd microspheres. Caspase-3-positive cell profiles were increased in the post-ischemic kidneys (p < 0.001) and increased as the length of ischemia increased (p = 0.003). In both WI₁₂₀and WI₂₄₀, the amount of^99mTc-sestamibi in the ischemic kidney was significantly lower than the amount of¹⁵³Gd microspheres (40 ± 5 versus 51 ± 5 and 20 ± 11 versus 27 ± 17;p < 0.05).Conclusions: In an established pig model with unilateral renal warm ischemia, we found significantly reduced^99mTc-sestamibi uptake relative to perfusion in the kidneys exposed to ischemia indicating a potential ability to detect renal ischemic and reperfusion injuries. However, apoptosis was not detected using^99mTc-lactadherin in the post-ischemic kidneys despite increased number of caspase-3-positive cell profiles.Trial registration: This study is approved by the Danish Inspectorate of Animal Experiments (2010/561-1837).

Glomerular filtration rates for individual kidneys can be measured semi-quantitatively by a gamma camera using [^99mTc]Tc-DTPA, with limited diagnostic accuracy. A more precise measurement can be performed on a PET/CT scanner using the radiotracer [⁶⁸Ga]Ga-EDTA, which has been validated in animal studies. The purpose of this study was to develop an easy kit-based synthesis of [⁶⁸Ga]Ga-EDTA that is compliant with good manufacturing practice (GMP) and applicable for human use. The production of the cold kit and its labeling were validated, as were the radiochemical purity measurement and analytical procedures for determining the Na₂EDTA dihydrate content in the kits. In this study, we validated a GMP kit for the simple production of [⁶⁸Ga]Ga-EDTA, with the intention of applicability for human use.