Side-by-side comparison of the two widely studied GRPR radiotracers, radiolabeled NeoB and RM2, in a preclinical setting.

INTRODUCTION: NeoB and RM2 are the most investigated gastrin-releasing peptide receptor (GRPR)-targeting radiotracers in preclinical and clinical studies. Therefore, an extensive side-by-side comparison of the two radiotracers is valuable to demonstrate whether one has advantages over the other. Accordingly, this study aims to compare the in vitro and in vivo characteristics of radiolabeled NeoB and RM2 to guide future clinical studies. METHOD: The stability of the radiolabeled GRPR analogs was determined in phosphate buffered saline (PBS), and commercially available mouse and human serum. Target affinity was determined by incubating human prostate cancer PC-3 cells with [177Lu]Lu-NeoB or [177Lu]Lu-RM2, + / - increasing concentrations of unlabeled NeoB, RM2, or Tyr4-bombesin (BBN). To determine uptake and specificity cells were incubated with [177Lu]Lu-NeoB or [177Lu]Lu-RM2 + / - Tyr4-BBN. Moreover, in vivo studies were performed to determine biodistribution and pharmacokinetics. Finally, radiotracer binding to various GRPR-expressing human cancer tissues was investigated. RESULTS: Both radiotracers demonstrated high stability in PBS and human serum, but stability in mouse serum decreased substantially over time. Moreover, both radiotracers demonstrated high GRPR affinity and specificity, but a higher uptake of [177Lu]Lu-NeoB was observed in in vitro studies. In vivo, no difference in tumor uptake was seen. The most prominent difference in uptake in physiological organs was observed in the GRPR-expressing pancreas; [177Lu]Lu-RM2 had less pancreatic uptake and a shorter pancreatic half-life than [177Lu]Lu-NeoB. Furthermore, [177Lu]Lu-RM2 presented with a lower tumor-to-kidney ratio, while the tumor-to-blood ratio was lower for [177Lu]Lu-NeoB. The autoradiography studies revealed higher binding of radiolabeled NeoB to all human tumor tissues. CONCLUSION: Based on these findings, we conclude that the in vivo tumor-targeting capability of radiolabeled NeoB and RM2 is similar. Additional studies are needed to determine whether the differences observed in physiological organ uptakes, i.e., the pancreas, kidneys, and blood, result in relevant differences in organ absorbed doses when the radiotracers are applied for therapeutic purposes.

Two bifunctional desferrioxamine chelators for bioorthogonal labeling of biovectors with zirconium-89.

We report two bifunctional chelators, DFO-Cys and DFO-CBT, to label biovectors with zirconium-89 according to the 2-cyanobenzothiazole/1,2-aminothiol cycloaddition. Their features are high labeling yields, rapid and efficient bioconjugation, metabolically stable luciferin-based end products, and applicability to orthogonal two-step labeling of sensitive biomolecules.

Combined evaluation of myocardial perfusion and coronary morphology in the identification of subclinical CAD. Radiation exposure of 13N-ammonia PET/CT.

PURPOSE: to evaluate the mean effective radiation dose of 13N-ammonia PET/CT and ECG-pulsing CT angiography (CTA) in the evaluation of myocardial perfusion, myocardial blood flow (MBF) and coronary morphology for the identification of subclinical CAD. PATIENTS, MATERIAL, METHODS: following rest-stress 13N-ammonia PET/CT perfusion imaging and MBF quantification, ECG-pulsing CTA at a pulse window of 70% of the R-R cycle was performed in ten healthy controls and in sixteen individuals with cardiovascular risk factors. Individual radiation dose exposure for ECG-pulsing CTA was estimated from the dose-length product. RESULTS: PET demonstrated normal perfusion in all study individuals, while hyperemic MBFs during dipyridamole stimulation and the myocardial flow reserve (MFR) in cardiovascular risk individuals were significantly lower than in healthy controls (1.34±0.26 vs. 2.28±0.47 ml/g/min and 1.48±0.39 vs. 3.24±0.81, both p≤0.0001). Further, ECG-pulsing CTA identified mild calcified and non-calcified coronary plaque burden in 7 (43%) individuals of the cardiovascular risk group. Rest-stress 13N-ammonia PET/CT perfusion study yielded a mean effective radiation dose of 3.07±0.06 mSv (2.07±0.06 mSv from the rest-stress 13N-ammonia injections and 1.0 mSv from the 2 CT transmission scans), while ECG-pulsing CTA was associated with 5.57±2.00 mSv. The mean effective radiation dose of the combined 13N-ammonia PET/CT and ECG-pulsing CTA exams in the evaluation of myocardial perfusion and coronary morphology was 8.0±1.5 mSv. CONCLUSION: 13N-ammonia PET/CT and ECG-pulsing CTA affords cardiac hybrid imaging studies in the evaluation of subclinical CAD with a relatively low mean effective radiation exposure of 8.0±1.5mSv.

Gamma radiation effects on potassium pertechnetate in carbonate media.

Gamma radiation effects on the stability of the oxidation state of radioelements and diffusion within the framework of nuclear waste repositories are often neglected, although it may influence physicochemical processes and thus transfer to biosphere and geosphere. This knowledge is essential to model transport phenomena. This study reports on effects of gamma irradiation on technetium in carbonate media, which is representative of natural systems. Depending on media compositions, the gamma irradiation on pertechnetate leads to formation of Tc(IV) only in the absence of carbonate. CO3*- radicals are able to re-oxidise technetium intermediate oxidation states to the +7 state.