Synthesis of 18F-labelled 2-fluoro-1,4-quinones using acetylhypofluorite

The fluorination of 1,4-benzo- and naphthoquinones using [18F]acetylhypofluorite is described. For compounds with electron-donating substituents fair to good radiochemical yields have been reached

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

The promise of immuno-PET in radioimmunotherapy

Immuno-PET as a quantitative imaging procedure before or concomitant with radioimmunotherapy is an attractive option to improve confirmation of tumor targeting and especially assessment of radiation dose delivery to both tumor and normal tissues. General information about PET, PET systems, and quantification is provided in this review. The requirements for an appropriate positron emitter and characteristics of the most attractive candidate emitters for immuno-PET are discussed. An overview of preclinical and clinical immuno-PET studies reported in the literature is provided

Basic principles, applications in oncology and improved selectivity of photodynamic therapy

Photodynamic therapy (PDT) is a promising approach for the treatment of superficially localized tumors. This review starts with a summary of the basic principles of PDT, in which the current practice, the photochemical mechanisms, cellular and subcellular targets, as well as the most prominent photosensitizers are discussed. Next, the clinical results obtained with PDT for the treatment of a variety of tumor types are outlined. Unfortunately, most of these studies revealed a lack of tumor selectivity of the photosensitizers, which resulted in prolonged skin photosensitivity and severe normal tissue toxicity. The last section of this review, therefore, focuses on novel strategies designed to improve the tumor selectivity of photosensitizers

High-quality 124I-labelled monoclonal antibodies for use as PET scouting agents prior to 131I-radioimmunotherapy

Purpose: Monoclonal antibodies (MAbs) labelled with 124I are an attractive option for quantitative imaging with positron emission tomography (PET) in a scouting procedure prior to 131I-radioimmunotherapy ( 131I-RIT). In this study, three important items in the labelling of MAbs with 124I were introduced to obtain optimal and reproducible product quality: restoration of radiation-induced inorganic deterioration of the starting 124I solution, radiation protection during and after 124I labelling, and synchronisation of the I/MAb molar ratio. Methods: A new method was applied, using an NaIO3/ NaI carrier mix, realising in one step >90% restoration of deteriorated 124I into the iodide form and chemical control over the I/MAb molar ratio. Chimeric MAb (cMAb) U36 and the murine MAbs 425 and E48 were labelled with 124I using the so-called lodogen-coated MAb method, as this method provides optimal quality conjugates under challenging radiation conditions. As a standardising condition, NaIO3/NaI carrier mix was added at a stoichiometric I/MAb molar ratio of 0.9. For comparison, MAbs were labelled with 131I and with a mixture of 124I, 123I, 126I and 130I. Results: Labelling with 124I in this setting resulted in overall yields of >70%, a radiochemical purity of >95%, and preservation of MAb integrity and immunoreactivity, including at the patient dose level (85 MBq). No significant quality differences were observed when compared with 131I products, while the iodine isotope mixture gave exactly the same labelling efficiency for each of the isotopes, excluding a different chemical reactivity of 124I-iodide. The scouting performance of 124I-cMAb U36 la-belled at the patient dose level was evaluated in biodistribution studies upon co-injection with 131I- labelled cMAb U36, and by PET imaging in nude mice bearing the head and neck cancer xenograft line HNX-OE. 124I-cMAb and 131I-cMAb U36 labelled with a synchronised I/MAb molar ratio gave fully concordant tissue uptake values. Selective tumour uptake was confirmed with immuno-PET, revealing visualisation of 15 out of 15 tumours. Conclusion: These results pave the way for renewed evaluation of the potential of 124I-immuno-PET for clinical applications

Comparison of aluminium (III) phthalocyanine tetrasulfonate- and meta-tetrahydroxyphenylchlorin-monoclonal antibody conjugates for their efficacy in photodynamic therapy in vitro

A challenge in photodynamic therapy (PDT) is to improve the tumour selectivity of the photosensitizers by using monoclonal antibodies (MAbs). With this aim, we developed MAb-conjugates with the hydrophobic photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC) and with the hydrophilic sensitizer aluminium (III) phthalocyanine tetrasulfonate (AI-PCS4). The capacity of these photoimmunoconjugates for selective targeting of squamous cell carcinoma (SCC) in vivo was demonstrated previously in SCC-bearing nude mice. Preliminary in vitro PDT studies with the vulvar SCC cell line A431 showed promising phototoxicity with both sensitizers when coupled to the internalizing MAb 42S. To rank the photosensitizers for their potential in photoimmunotherapy, we herein describe an extensive in vitro evaluation of mTHPC-MAb and AIPcS4-MAb conjugates. Both classes of conjugates were directly compared using 5 different SCC cell lines as target and 3 different MAbs (BIWA 4, E48 and 425) for tumour cell targeting. In contrast to free AIPcS4 (IC50 ≥ 700 nM), MAb-conjugated AIPcS4 was found to be highly phototoxic in PDT in all 5 cell lines. AIPcS4-BIWA 4 was most consistently effective with IC50 values ranging from 0.06-5.4 nM. mTHPC-MAb conjugates were in general hardly effective. Phototoxicity (log IC50) of the AIPcS4-MAb conjugates was found to be strongly correlated with their total cell binding capacity (internalized and surface bound) and to be less correlated with their internalization capacity. In conclusion, these data show a high potential of AIPcS4-MAb conjugates in comparison to mTHPC-MAb conjugates for use in PDT

Synthesis and evaluation of 99mTc/99Tc-MAG3-biotin conjugates for antibody pretargeting strategies

Four 99mTc-MAG3-biotin conjugates were synthesized to determine their potential use in antibody pretargeting strategies for radioimmunoscintigraphy (RIS). To use these 99mTc-MAG3-biotin conjugates as model compounds for 186Re-MAG3-biotin conjugates for radioimmunotherapy (RIT), nanomolar amounts of 99Tc were added as carrier to 99mTc. The biotin derivatives used for the preparation of the conjugates - biocytin, biotin hydrazide, biotinyl-piperazine, and biotinyl-diaminosuccinic acid - differed at the site that is regarded to be susceptible to hydrolysis by biotinidase present in human plasma. All four conjugates were produced with high radiochemical purity, were stable in PBS, and demonstrated full binding capacity to streptavidin. The 99mTc/99Tc-MAG3-labeled biotinyl-piperazine and biotinyl-diaminosuccinic acid conjugates were stable in mouse as well as human plasma, whereas the corresponding biocytin and biotin hydrazide conjugates were rapidly degraded. The biodistribution in nude mice at 30 min after injection was similar for all conjugates, and a rapid blood clearance and high intestinal excretion were both observed. It is concluded that the metabolic routing of a conjugate containing biotin and MAG3 is dominated by these two moieties. For this reason, MAG3-biotin conjugates do not seem suited for pretargeted RIT, for which quantitative and fast renal excretion is a prerequisite to minimize radiation toxicity. However, in a pretargeted RIS approach the 99mTc-MAG3-biotin conjugates might have potential