Early differences in dynamic uptake of 68Ga-PSMA-11 in primary prostate cancer: A test-retest study.

INTRODUCTION: Dynamic PET/CT allows visualization of pharmacokinetics over the time, in contrast to static whole body PET/CT. The objective of this study was to assess 68Ga-PSMA-11 uptake in pathological lesions and benign tissue, within 30 minutes after injection in primary prostate cancer (PCa) patients in test-retest setting. MATERIALS AND METHODS: Five patients, with biopsy proven PCa, were scanned dynamically in list mode for 30 minutes on a digital PET/CT-scanner directly after an intravenous bolus injection of 100 MBq 68Ga-PSMA-11. Approximately 45 minutes after injection a static whole body scan was acquired, followed by a one bed position scan of the pelvic region. The scans were repeated approximately four weeks later, without any intervention in between. Semi-quantitative assessment was performed using regions-of-interest in the prostate tumor, bladder, gluteal muscle and iliac artery. Time-activity curves were extracted from the counts in these regions and the intra-patient variability between both scans was assessed. RESULTS: The uptake of the iliac artery and gluteal muscle reached a plateau after 5 and 3 minutes, respectively. The population fell apart in two groups with respect to tumor uptake: in some patients the tumor uptake reached a plateau after 5 minutes, whereas in other patients the uptake kept increasing, which correlated with larger tumor volumes on PET/CT scan. Median intra-patient variation between both scans was 12.2% for artery, 9.7% for tumor, 32.7% for the bladder and 14.1% for the gluteal muscle. CONCLUSION: Dynamic 68Ga-PSMA-11 PET/CT scans, with a time interval of four weeks, are reproducible with a 10% variation in uptake in the primary prostate tumor. An uptake plateau was reached for the iliac artery and gluteal muscle within 5 minutes post-injection. A larger tumor volume seems to be related to continued tumor uptake. This information might be relevant for both response monitoring and PSMA-based radionuclide therapies.

Ultra-trace Cu isotope ratio measurements via multi-collector ICP-mass spectrometry using Ga as internal standard: an approach applicable to micro-samples.

The capabilities of Cu isotope ratio measurements are often restricted by the small volumes of sample available and/or their low Cu concentration. In this work, an analytical approach was developed for performing Cu isotopic analysis via multi-collector ICP-mass spectrometry (MC-ICP-MS) at ultra-trace level using Ga as an internal standard for mass bias correction. The minimum concentration of Cu required for accurate and precise isotope ratio measurements was established to be 20 µg L-1 with wet plasma conditions and 5 µg L-1 with dry plasma conditions. The use of Ga as an internal standard for mass bias correction provided several advantages compared to Ni, i.e. improved internal precision on δ65Cu values and lower blank levels. Ga can also be used at a 4-fold lower concentration level than Ni. However, in wet plasma conditions, the signals of 36Ar16O21H+ and 40Ar15N16O+ interfered with the signals of 69Ga+ and 71Ga+, respectively, while in dry plasma conditions, realized by the use of a desolvation unit, 69Ga+ suffered from spectral interference from 40Ar14N21H+. These interferences were resolved by using medium mass resolution. For validation purposes, the approach was applied to commercially available blood and serum samples. The δ65Cu values for the samples measured at a concentration level of 5 µg L-1 Cu and 5 µg L-1 Ga using dry plasma conditions were in good agreement with those obtained for isotope ratio measurements at the "standard" concentration level of 200 µg L-1 Cu and 200 µg L-1 Ni using wet plasma conditions. In addition, the δ65Cu values obtained for micro-samples of serum/blood (volume of 100 µL) were in good agreement with the corresponding ones obtained using the "standard" volume for isotopic analysis (500 µL).

Gallium and its competing roles with iron in biological systems.

Gallium, a group IIIa metal, shares chemical properties with iron. Studies have shown that gallium-based compounds have potential therapeutic activity against certain cancers and infectious microorganisms. By functioning as an iron mimetic, gallium perturbs iron-dependent proliferation processes in tumor cells. Gallium's action on iron homeostasis leads to disruption of ribonucleotide reductase, mitochondrial function, and the regulation of transferrin receptor and ferritin. In addition, gallium nitrate stimulates an increase in mitochondrial reactive oxygen species in cells which triggers downstream upregulation of metallothionein and hemoxygenase-1. Gallium's anti-infective activity against bacteria and fungi results from disruption of microbial iron utilization through mechanisms which include gallium binding to siderophores and downregulation of bacterial iron uptake. Gallium compounds lack cross-resistance to conventional chemotherapeutic drugs and antibiotics thus making them attractive agents for drug development. This review will focus on the mechanisms of action of gallium with emphasis on its interaction with iron and iron proteins.