TY - JOUR AB - Flatworms of the species Schmidtea mediterranea are immortal-adult animals contain a large pool of pluripotent stem cells that continuously differentiate into all adult cell types. Therefore, single-cell transcriptome profiling of adult animals should reveal mature and progenitor cells. By combining perturbation experiments, gene expression analysis, a computational method that predicts future cell states from transcriptional changes, and a lineage reconstruction method, we placed all major cell types onto a single lineage tree that connects all cells to a single stem cell compartment. We characterized gene expression changes during differentiation and discovered cell types important for regeneration. Our results demonstrate the importance of single-cell transcriptome analysis for mapping and reconstructing fundamental processes of developmental and regenerative biology at high resolution. AU - Fiedler, L.* AU - Kellner, M. AU - Gosewisch, A.* AU - Oos, R.* AU - Böning, G.* AU - Lindner, S.* AU - Albert, N.* AU - Bartenstein, P.* AU - Reulen, H.J.* AU - Zeidler, R. AU - Gildehaus, F.J.* C1 - 53294 C2 - 44547 CY - 1200 New York Ave, Nw, Washington, Dc 20005 Usa SP - 55-62 TI - Evaluation of 177Lu[Lu]-CHX-A″-DTPA-6A10 Fab as a radioimmunotherapy agent targeting carbonic anhydrase XII. JO - Nucl. Med. Biol. VL - 60 PB - Amer Assoc Advancement Science PY - 2018 SN - 0969-8051 ER - TY - JOUR AB - INTRODUCTION: This work develops a compartmental model of (18)F-choline in order to evaluate its biokinetics and so to describe the temporal variation of the radiopharmaceuticals' uptake in and clearance from organs and tissues. METHODS: Ten patients were considered in this study. A commercially available tool for compartmental analysis (SAAM II) was used to model the values of activity concentrations in organs and tissues obtained from PET images or from measurements of collected blood and urine samples. RESULTS: A linear compartmental model of the biokinetics of the radiopharmaceutical was initially developed. It features a central compartment (blood) exchanging with organs. The structure describes explicitly liver, kidneys, spleen, blood and urinary excretion. The linear model tended to overestimate systematically the activity in the liver and in the kidney compartments in the first 20 min post-administration. A nonlinear process of kinetic saturation was considered, according to the typical Michaelis-Menten kinetics. Therefore nonlinear equations were added to describe the flux of (18)F-choline from blood to liver and from blood to kidneys. The nonlinear model showed a tendency for improvement in the description of the activity in liver and kidneys, but not for the urine. CONCLUSIONS: The simple linear model presented is not able to properly describe the biokinetics of (18)F-choline as measured in prostatic cancer patients. The introduction of nonlinear kinetics, although based on physiologically plausible assumptions, resulted in nonsignificant improvements of the model predictive power. AU - Tavola, F.* AU - Janzen, T. AU - Giussani, A. AU - Facchinetti, D.* AU - Veronese, I.* AU - Uusijärvi-Lizana, H.* AU - Mattsson, S.* AU - Hoeschen, C. AU - Cantone, M.C.* C1 - 7156 C2 - 29496 SP - 261-268 TI - Nonlinear compartmental model of 18F-choline. JO - Nucl. Med. Biol. VL - 39 IS - 2 PB - Elsevier PY - 2012 SN - 0969-8051 ER - TY - JOUR AB - The mouse monoclonal antibody MOv18, directed against the alpha-isoform of folate receptor (FR), was investigated to identify the optimal radioconjugate for radioimmunotherapy of minimal residual disease in ovarian cancer. Methods: Pharmacokinetics, biodistribution, long-term therapeutic efficacy and toxicity of MOv18, labeled with the beta-emitters I-131, Y-90 and Lu-177, were compared in a xenografted mouse model, composed by two cell lines, A431FR and A431MK, differing only for FR expression. Results: A shorter blood clearance and a higher tumor uptake were observed for Y-90- and Lu-177- compared to I-131-MOv18, and a shorter blood pharmacokinetics was recorded in A431FR-bearing animals. At equitoxic maximum tolerable doses, the general irradiation by I-131- and Y-90-MOv18 gives rise to strong targeted effects on A431FR and nontargeted effects on A431MK tumors, while Lu-177-MOv18 was able to eradicate small size tumor masses expressing the antigen of interest exerting only mild non-targeted effects. Conclusion: Lu-177-MOv18 at the maximal tolerated dose is the immunoradioconjugate with the best therapeutic window in experimental conditions of small tumor volume. AU - Zacchetti, A.* AU - Coliva, A.* AU - Luison, E.* AU - Seregni, E.* AU - Bombardieri, E. AU - Giussani, A. AU - Figini, M.* AU - Canevari, S.* C1 - 328 C2 - 26636 CY - New York SP - 759-770 TI - 177Lu-labeled MOv18 as compared to 131I- or 90Y-labeled MOv18 has the better therapeutic effect in eradication of alpha folate receptor-expressing tumor xenografts. JO - Nucl. Med. Biol. VL - 36 IS - 7 PB - Elsevier Science Inc PY - 2009 SN - 0969-8051 ER -