[99mTc]Tc-DB15 in GRPR-Targeted Tumor Imaging with SPECT: From Preclinical Evaluation to the First Clinical Outcomes

Diagnostic imaging and radionuclide therapy of prostate (PC) and breast cancer (BC) using radiolabeled gastrin-releasing peptide receptor (GRPR)-antagonists represents a promising approach. We herein propose the GRPR-antagonist based radiotracer [99mTc]Tc-DB15 ([99mTc]Tc-N4-AMA-DGA-DPhe6,Sar11,LeuNHEt13]BBN(6-13); N4: 6-carboxy-1,4,8,11-tetraazaundecane, AMA: aminomethyl-aniline, DGA: diglycolic acid) as a new diagnostic tool for GRPR-positive tumors applying SPECT/CT. The uptake of [99mTc]Tc-DB15 was tested in vitro in mammary (T-47D) and prostate cancer (PC-3) cells and in vivo in T-47D or PC-3 xenograft-bearing mice as well as in BC patients. DB15 showed high GRPR-affinity (IC50 = 0.37 ± 0.03 nM) and [99mTc]Tc-DB15 strongly bound to the cell-membrane of T-47D and PC-3 cells, according to a radiolabeled antagonist profile. In mice, the radiotracer showed high and prolonged GRPR-specific uptake in PC-3 (e.g., 25.56 ± 2.78 %IA/g vs. 0.72 ± 0.12 %IA/g in block; 4 h pi) and T-47D (e.g., 15.82 ± 3.20 %IA/g vs. 3.82 ± 0.30 %IA/g in block; 4 h pi) tumors, while rapidly clearing from background. In patients with advanced BC, the tracer could reveal several bone and soft tissue metastases on SPECT/CT. The attractive pharmacokinetic profile of [99mTc]DB15 in mice and its capability to target GRPR-positive BC lesions in patients highlight its prospects for a broader clinical use, an option currently being explored by ongoing clinical studies.

Separation of Rare Earth Elements (REE) by Ion Interaction Chromatography (IIC) Using Diglycolic Acid (ODA) as a Complexing Agent

The possibility of rare earth elements (REE) separation by ion interaction chromatography (IIC) employing their complexes with diglycolic acid (ODA) in anion exchange mode has been studied theoretically and experimentally. Calculations, assuming that only trivalent complex is significantly uptaken by the stationary phase, indicated that at at pH 4–6, the retention in the lanthanide series should increase from La to the Tb–Dy–Ho region with yttrium showing apparent atomic number (App.At.No.) of 67½ and then decrease with further increase of atomic number. Chromatographic experiments in the system: Column: Eternity C18—mobile phase 5 mM ODA/8.6 mM TBAOH/0.6 mM HNO3; pH 4.60 confirmed theoretically predictions. It was found that scandium at pH ≥ 4.0 elutes in front of the whole REE group but at low pH enters the region of light lanthanides. The non-monotonical change of affinity of the REE with the increase of atomic number results in quite unusual order of elution of REE namely: Sc < La < Ce < Lu < Pr < Yb < Nd < Tm < Sm < Eu < Er≈Y < Gd < Ho < Tb≈Dy.

Analysis of Diglycolic Acid after Mass Poisoning by Diethylene Glycol

In December 2019, unusual cases of acute renal failure with neurological changes were observed in the State of Minas Gerais, Brazil. Criminal investigations indicated cases of intoxication after consumption of beers contaminated with diethylene glycol (DEG). The elimination of DEG by the body is fast, but its metabolite, diglycolic acid (DA), may persist for a long time. To assess the level of intoxicated victims who consumed the contaminated beers, qualitative and quantitative methods were developed to determine DA in biological matrices by gas chromatography coupled to a mass spectrometer (GC–MS) and gas chromatography coupled to a mass spectrometer with triple-quadrupole mass filter (GC–MS-MS), respectively. The validated qualitative method presents good selectivity and limit of detection of 1 µg/mL (whole blood, urine, vitreous humor and cerebrospinal fluid) and 5 µg/g (liver and kidney), respectively. A quantitative method for whole blood presented satisfactory performance to determine DA. Twelve victims presented positive results for DA in whole blood, with concentrations ranging from 2 to 108 µg/mL. The toxicology laboratory of the Institute of Forensic Medicine of Minas Gerais was the first governmental agency to identify DA in whole blood, vitreous humor, cerebrospinal fluid, kidney and urine in victims affected by this contaminant. The results of this study legally supported the prohibition of the continued consumption of the beer and avoided further intoxications. Our results showed, for real cases of human intoxication, that DA can still be detected in alternative matrices, even when non-detectable in blood, demonstrating the importance of collecting different kinds of samples for a proper investigation.