Optimization of Automated Radiosynthesis of Gallium-68-Labeled PSMA11 with Two [68Ge]Ge/[68Ga]Ga Generators: Fractional Elution or Prepurification?

Prostate cancer is one of the most common forms of cancer in men. An imaging technique for its diagnosis is [68Ga]-prostate-specific membrane antigen ([68Ga]Ga-PSMA-11) positron emission tomography (PET). To address the increasing demand for [68Ga]-labeled peptides and reduce the cost of radiosynthesis, it is therefore necessary to optimize the elution process of [68Ge]Ge/[68Ga]Ga generators. This study aims to identify the most effective approach for optimizing radiosynthesis using double elution in parallel of two [68Ge]Ge/[68Ga]Ga generators. Two methods have been tested: one using prepurification, and the other using fractionated elution. Five synthesis sequences were conducted using each method. The mean labeling yields for double elution with prepurification were 45.8 ± 29.4 (mean ± standard deviation) and none met the required criteria. The mean labeling yields for the fractionated double elution were 97.5 ± 1.9 (mean ± standard deviation) meeting the criteria, significantly superior to the prepurification method (p = 0.012), and similar to those of simple elution. This study showed that fractionated double elution from [68Ge]Ge/[68Ga]Ga generators produced a significantly higher labeling yield than double elution with prepurification, resulting in a larger activity recovered via radiosynthesis, thereby allowing more diagnostic tests to be performed.

Management of Patients with Renal Failure Undergoing Dialysis During 131I Therapy for Thyroid Cancer.

Radioactive iodine (131I) therapy may be used to treat thyroid cancer in end-stage renal disease patients who undergo hemodialysis. Because iodine uses predominantly renal clearance, treatment management in hemodialysis patients may be problematic, and no formal recommendations on hemodialysis currently exist. This work details our experience with treating thyroid cancer with iodine in chronic renal failure patients who require hemodialysis and details the dosimetry results obtained during treatment to ensure that the dose to the bone marrow (BM) was acceptable. Methods: We treated 6 patients in the metabolic radiotherapy unit after thyroid stimulation. Two hemodialysis sessions in the metabolic radiotherapy unit were performed at 42 and 90 h after radiopharmaceutical administration. BM toxicity was estimated with activity measurements from blood samples and with whole-body measurements that were regularly repeated during hospitalization and measured with a γ-counter. The patients underwent thyroid and hematologic monitoring to assess treatment efficacy and therapeutic toxicity in the short, medium, and long term. Results: Whole-body activity was reduced on average by 66.7% (range, 60.1%-71.5%) after the first dialysis session and by 53.3% (range, 30.4%-67.8%) after the second. The mean estimated total absorbed dose to the BM was 0.992 Gy for all patients (range, 0.431-2.323 Gy). We did not observe any significant hematologic toxicity, and the clinical, biologic, and ultrasound test results confirmed the success of ablative treatment for most patients. Conclusion: In hemodialysis patients with thyroid cancer, an 131I activity approximately 30% lower than the nominal dose appears to strike an appropriate balance between absence of BM toxicity and therapeutic efficacy. To avoid overirradiation, we recommend pretherapeutic dosimetry studies for metastatic patients to calculate the amount of activity to be administered. We also recommend dosimetry monitoring during the hemodialysis sessions performed after therapeutic dose administration and under the same conditions.

Potential Impact of Infusion Technique on Drug Delivery.

BACKGROUND: Infusion practices have been modified, especially for antineoplastic drugs, through the use of specific infusion devices with postadministration rinsing (PAR) so as to decrease occupational exposure to drugs. The aim of this study was to highlight how such infusion devices may impact the drug delivery of injectable drugs. MATERIALS AND METHODS: Drug infusions were simulated with a radiotracer (99mTc) for 30 minutes to assess nine different infusion lines: 2 infusion methods without PAR (1 gravity-fed infusion and 1 pump infusion), 2 extension lines to be connected to standard infusion devices to allow PAR, and 5 specific infusion sets allowing a PAR. 99mTc was compounded in 250 or 100 mL of 0.9% NaCl solution. From the continuous recording of drug concentrations at device outlets, the areas under the drug concentration-time curve (AUC) were computed and divided in 2 parts: the AUCadm corresponding to the administration phase and the AUCrin corresponding to the rinsing phase. Their comparison to the initial activity led to compute the drug delivery. Results between groups were compared using a Kruskal-Wallis test (P < 0.05). RESULTS: Using standard infusion devices leads to administer only 91% and 88% when the drug is diluted in 250 and 100 mL, respectively. During the administration phase with the extension lines connected to infusion sets, between 90.8 ± 6.9% and 94.2 ± 1.8% of the drug is infused for 250 mL dilutions and 87.7 ± 2.0% for 100 mL dilutions. For specific infusion sets, the proportion of infused drug varied between 88.6 ± 6.0% and 95.3 ± 1.5% for dilutions in 250 mL and 71.2 ± 3.1% and 90.4 ± 2.8% for dilutions in 100 mL. Rinsing the lines means the remaining drug is administered a rinsing volume ranging between 47.0 ± 6.6 and 92.2 ± 8.9 mL according to the device and drug dilution. CONCLUSIONS: This study shows that drug delivery may differ according to infusion line and dilution volume. Further study is required to assess the impact of these devices on pharmacokinetics.

Theory of surface micelles of semifluorinated alkanes.

Surface structures of semifluorinated alkanes F(CF(2))(n)(CH(2))(m)H (referred to as FnHm) spread on the air/water interface are investigated theoretically. The study is focused on the disklike surface micelles that were recently identified by AFM and scattering techniques at sufficiently high surface concentrations. We show that (1) the micelles emerge as a result of liquid/liquid (rather than liquid/gas) phase separation in the Langmuir layer; (2) the micelles are islands of the higher-density phase with roughly vertical orientation of FnHm molecules (F-parts extend toward air, H-parts toward water) and the matrix is the lower density-phase where the FnHm diblocks are nearly parallel to the water surface; (3) the micelles and the hexagonal structure they form are stabilized by the electrostatic interactions which are mainly due to the vertical dipole moments of the CF(2)- CH(2) bonds in the vertical phase; and (4) the electrostatic repulsive interactions can serve to suppress the micelle size polydispersity.

Structural studies of the neural-cell-adhesion molecule by X-ray and neutron reflectivity.

The structures of adhesion proteins play an important role in the formation of intercellular junctions and the control of intermembrane spacing. This paper describes the combination of neutron and X-ray specular reflectivity measurements to investigate the structure of the ectodomain of the neural-cell-adhesion molecule (NCAM). The measurements with unmodified NCAM suggest the presence of a bend in the extracellular region. Measurements with the polysialic-acid-modified form of NCAM reveal that, at physiological ionic strength, the carbohydrate chains extend beyond the range of the unmodified protein. The excluded volume of the polymer is also ionic-strength-dependent, as expected for a polyelectrolyte. The structural characteristics obtained from these independent analyses of X-ray and neutron reflectivity data agree with each other, with prior reflectivity studies, and with molecular dimensions obtained from direct-force measurements. These results provide structural insights into the configuration of the NCAM ectodomain and the regulation of NCAM adhesion by post-translational modification.

A soluble VE-cadherin fragment forms 2D arrays of dimers upon binding to a lipid monolayer.

A high concentration of cadherin molecules at cell-cell adhesion sites is believed to be essential for generating strong intercellular junctions. In order to determine the interactions of cadherin domains involved in the early stages of lateral cluster formation on the cell surface, a recombinant fragment encompassing the first four domains of human VE-cadherin with a His-tag at the C terminus (VE-EC1-4-His) was produced. Two-dimensional crystals of VE-EC1-4-His were formed at the air-water interface using conventional lipids modified to contain a Ni(2+)-chelating group, which provides a specific site for interaction with the polyhistidine tag. The VE-EC1-4-His was monomeric at the concentration employed for crystal formation; however, the crystals exhibited a p2 symmetry and the presence of cis-dimer interactions between symmetry-related molecules. The VE-EC1-4-His molecules in the crystalline array have a remarkably compact conformation in contrast to the elongated "string of pearls" conformation seen in the hexameric assembly of VE-EC1-4-His in solution, and as seen in the crystal structure of C-cadherin. These results indicate that VE-cadherin can exist in at least two oligomeric states with different interactions between domains and can adopt highly different conformational states. We suggest that the compact cis-dimeric state may occur on isolated cells and that the compact form may serve to protect the molecule from degradation. As previously proposed we suppose that the trans-hexameric form is involved in intercellular adhesion.