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A full understanding concerning the photophysical properties of a fluorescent label is crucial for a reliable and predictable performance in biolabelling applications. This holds true not only for the choice of a fluorophore in general, but also for the correct interpretation of data, considering the complexity of biological environments. In the frame of a case study involving inflammation imaging, we report the photophysical characterization of four fluorescent S100A9-targeting compounds in terms of UV-vis absorption and photoluminescence spectroscopy, fluorescence quantum yields (ΦF) and excited state lifetimes (τ) as well as the evaluation of the radiative and non-radiative rate constants (kr and knr, respectively). The probes were synthesized based on a 2-amino benzimidazole-based lead structure in combination with commercially available dyes, covering a broad color range from green (6-FAM) over orange (BODIPY-TMR) to red (BODIPY-TR) and near-infrared (Cy5.5) emission. The effect of conjugation with the targeting structure was addressed by comparison of the probes with their corresponding dye-azide precursors. Additionally, the 6-FAM and Cy5.5 probes were measured in the presence of murine S100A9 to determine whether protein binding influences their photophysical properties. An interesting rise in ΦF upon binding of 6-FAM-SST177 to murine S100A9 enabled the determination of its dissociation equilibrium constant, reaching up to KD = 324 nM. This result gives an outlook for potential applications of our compounds in S100A9 inflammation imaging and fluorescence assay developments. With respect to the other dyes, this study demonstrates how diverse microenvironmental factors can severely impair their performance while rendering them poor performers in biological media, showing that a preliminary photophysical screening is key to assess the suitability of a particular luminophore.

Salvage surgery after radiation therapy is known to be associated with a high incidence of postoperative complications. We describe a case of a successful salvage surgery after BNCT. In our patient with head and neck carcinoma, cervical lymph node recurrence with adhesion to a large vessel occurred after conventional radiotherapy. This lesion responded well to BNCT. Salvage surgery was subsequently performed to remove the residual tumor. Histopathologically, the isolated tissue contained tumor cells in its center and the surrounding tissue showed severe fibrosis. However, the tissue outside of the irradiation area had almost no fibrosis. BNCT may facilitate salvage surgery after radiotherapy because it causes less injury to the surrounding tissue than conventional radiotherapy. Our experience suggests that BNCT may be a feasible preoperative treatment in patients with inoperable lesions or in those who strongly desire preservation of function.

OBJECTIVE: Multiple myeloma (MM) is an incurable condition with variable clinical course. The study included a group of patients with especially poor-prognosis, individuals with relapsed/refractory multiple myeloma (RRMM) and specific cytogenetic disorders. Among the currently used therapies the ixazomib-lenalidomid-dexamethasone (IRd) is considered as a candidate to improve outcomes. The aim of the study was to evaluate the safety and efficacy of IRd regimen in the treatment of patients with RMMM.
METHODS: Nine patients aged 52-82 years who received ixazomib in the early access programme, were included in the study. All patients met the criteria for recurrent/relapsed MM and had high (t(4:14), t(14:16), del17p or +1q21) risk aberrations. Previous chemotherapy regimens included thalidomide and bortezomib. Median duration of exposure to ixazomib was 12 months.
RESULTS: One patient with multiple cytogenetic aberrations and extramedullary plasmocytoma died because of progression after two months of treatment. In the remaining patients, the objective response to treatment was reached, and in four cases it was qualified as a very good partial response (VGPR). Observed adverse effects included neutropenia, infections, and oedema (in three cases Grade 3). Eight patients continue treatment, in two cases the decision was made to reduce lenalidomide doses.
CONCLUSIONS: Preliminary results suggest potentially high efficacy and good safety profile of IRd therapy in patients with RRMM and unfavourable cytogenetics.

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The photophysical properties, especially the intersystem crossing (ISC) of two heavy-atom-free BODIPY derivatives with twisted π-conjugated frameworks (benzo[b]-fused BODIPY, BDP-B; and [a]phenanthrene-fused BODIPY, BDP-P), are studied with steady-state and time-resolved optical and electron paramagnetic resonance (TREPR) spectroscopic methods as well as with ADC(2) theoretical investigations. Interestingly, BDP-B has a planar π-conjugation framework, but it displays weaker UV-vis absorption (ε = 3.8 × 104 M-1 cm-1 at 569 nm) and fluorescence (ΦF < 0.1%), a short-lived singlet-excited state (fluorescence lifetime, τF = 0.2 ns), and a long-lived triplet state (τT = 132.3 μs). In comparison, the more twisted BDP-P shows stronger UV-vis absorption (ε = 9.8 × 104 M-1 cm-1 at 640 nm) and fluorescence (ΦF = 70%), longer singlet-excited-state lifetime (τF = 6.4 ns), and shorter triplet-state lifetime (τT = 18.9 μs). In contrast to helicenes (ΦT = ca. 90%), the ISC of BDP-P and BDP-B is nonefficient (ΦT < 23%). The electron spin selectivity of the ISC of the derivatives is different, manifested by the phase pattern of the TREPR spectra as AAEAEE and EEEAAA for BDP-B and BDP-P, respectively. The spatially confined T1 state wave function of the twisted molecule keeps the T1 state energy high (1.44-1.61 eV). A dark S1 state was identified for BDP-B. This work demonstrated that the twisted π-conjugated framework does not necessarily induce efficient ISC and we found a dark singlet state for BODIPY, which is rare.

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BACKGROUND: Tumor lysis syndrome (TLS) is an oncologic emergency, but its incidence in MM is rare. To our knowledge, ixazomib has not been associated with TLS in MM.
UNASSIGNED: The patient developed TLS after 10 days of treatment with ixazomib, accompanied by renal failure of hyperuricemia, hyperkalemia, and hyperphosphatemia.
UNASSIGNED: MM (type IgG λ) was diagnosed according to the diagnostic criteria established by the International Myeloma Working Group and classified stage IIA by the International Staging System. TLS was diagnosed after the patient met all three criteria of the Cairo-Bishop TLS scoring system.
METHODS: From April 8, 2017, the patient was treated with 3 courses of bortezomib, cyclophosphamide, and dexamethasone chemotherapy. From August 18, she received five courses of bortezomib combined with DCEP chemotherapy. On May 21, 2018 treatment was switched to lenalidomide, bortezomib, and dexamethasone for four courses. Ixazomib was started on October 10, 2018 with cyclophosphamide and dexamethasone. On October 19, 2018 vigorous intravenous hydration with sodium bicarbonate was initiated and peroral febuxostat was administered.
RESULTS: On October 19, changes in hematological indicators raised concern for TLS worsening kidney function and decreasing urine output. She refused renal replacement treatment for TLS-induced acute kidney injury. On October 26th, the patient died of respiratory failure.
CONCLUSIONS: This case highlights the need to vigilant for the occurrence of TLS in patients undergoing MM treatment with ixazomib. Higher baseline uric acid or creatinine, rapidly progressive anemia, and raised lactate dehydrogenase (LDH) and β2-microglobulin may be surrogate markers of TLS.

We sought to evaluate the activity and safety of carfilzomib-/ixazomib-containing combinations for patients with relapsed/refractory multiple myeloma (RRMM). We searched published reports including carfilzomib-/ixazomib-containing combinations for RRMM. Finally, we identified 11 prospective studies covering 2845 relapsed/refractory patients. Carfilzomib- and ixazomib-containing combinations respectively resulted in an impressive overall response rate (ORR 77 vs. 64%, P = 0.14), very good partial response or better (≥ VGPR 48 vs. 21%, P = 0.001), complete response or better (≥ CR 14 vs. 7%, P = 0.23), and clinical benefit rate (CBR 84 vs. 59%, P = 0.0002). Subgroup analysis showed that the carfilzomib (CFZ) +lenalidomide (LEN) + dexamethasone (DEX) triplet regimen resulted into similar response outcomes to those from CFZ + DEX doublet regimen in ORR (77 vs. 78%, P = 0.91), ≥VGPR (50 vs. 53%, P = 0.84), and ≥ CR (13 vs. 12%, P = 0.96) analysis in these previously heavily pretreated population. And, there were no statistically significant differences between IXA + LEN + DEX triplet regimen and CFZ + LEN + DEX triplet regimen in ORR (85 vs. 78%, P = 0.55), ≥ VGPR (37 vs. 53%, P = 0.19), and ≥ CR (18 vs. 12%, P = 0.70) analysis. There were favorable trend towards proteasome inhibitors (PIs) + IMiDs + DEX in comparison with PIs + alkylating agent + Dex in ORR (79 vs 49%, P < 0.00001), ≥ VGPR analysis (36 vs. 16%, P = 0.008), and ≥ CR (16 vs. 3%, P < 0.00001). Compared with current standard chemotherapy, carfilzomib containing combinations clearly improved overall survival (HR, 0.79; P = 0.01), progression free survival (HR, 0.61; P = 0.0001). Carfilzomib-/ixazomib-containing combinations produced clinical benefit for patients with R/RMM. PIs + IMiDs + DEX triplet regimens could be good options for such relapsed/refractory patients.

ortho-Carborane (1,2-C2B10H12) was found to be a carrier of protons in both mitochondrial and artificial lipid membranes, suggesting that this dicarborane can reversibly release hydrogen ions and diffuse through the membranes in neutral and anionic forms. Similar to conventional uncouplers (e.g. 2,4-dinitrophenol), o-carborane stimulated mitochondrial respiration and decreased the membrane potential at concentrations of tens of micromoles. Protonophoric activity of o-carborane was observed both by a fluorometric assay using pyranine-loaded liposomes and electrical current measurements across planar lipid bilayers. Substantial contribution of the proton flux to the o-carborane-mediated current was proved by a shift of the zero current voltage upon imposing a pH gradient across the membrane. Meta-carborane (1,7-C2B10H12) lacked the protonophoric activity in line with its reduced C-H acidity. The results suggest that weak C-H acids can exhibit protonophoric activity in the biological environment. The finding of a new class of protonophoric compounds is of substantial interest due to promising anti-obesity and anti-diabetic properties of uncouplers.