Biokinetics of Radiolabeled Monoclonal Antibody BC8: Differences in Biodistribution and Dosimetry Among Hematologic Malignancies.

We reviewed 111In-DOTA-anti-CD45 antibody (BC8) imaging and bone marrow biopsy measurements to ascertain the biodistribution and biokinetics of the radiolabeled antibody and to investigate differences based on type of hematologic malignancy. Methods: Serial whole-body scintigraphic images (4 time points) were obtained after infusion of the 111In-DOTA-BC8 (176-406 MBq) into 52 adult patients with hematologic malignancies (lymphoma, multiple myeloma, acute myeloid leukemia, and myelodysplastic syndrome). Counts were obtained for the regions of interest for spleen, liver, kidneys, testicles (in men), and 2 marrow sites (acetabulum and sacrum), and correction for attenuation and background was made. Bone marrow biopsies were obtained 14-24 h after infusion, and the percentage of administered activity was determined. Absorbed radiation doses were calculated. Results: Initial uptake in liver averaged 32% ± 8.4% (SD) of administered activity (52 patients), which cleared monoexponentially with a biologic half-time of 293 ± 157 h (33 patients) or did not clear (19 patients). Initial uptake in spleen averaged 22% ± 12% and cleared with a biologic half-time of 271 ± 185 h (36 patients) or longer (6 patients). Initial uptake in kidney averaged 2.4% ± 2.0% and cleared with a biologic half-time of 243 ± 144 h (27 patients) or longer (9 patients). Initial uptake in red marrow averaged 23% ± 11% and cleared with a biologic half-time of 215 ± 107 h (43 patients) or longer (5 patients). Whole-body retention half-time averaged 198 ± 75 h. Splenic uptake was higher in the AML/MDS group than in the lymphoma group (P ≤ 0.05) or the multiple myeloma group (P ≤ 0.10). Liver represented the dose-limiting organ. For liver uptake, no significant differences were observed among the 3 malignancy groups. Average calculated radiation absorbed doses per unit of administered activity for a therapy infusion of 90Y-DOTA-BC8 were 0.35 ± 0.20 cGy/MBq for red marrow, 0.80 ± 0.24 cGy/MBq for liver, 3.0 ± 1.4 cGy/MBq for spleen, 0.055 ± 0.014 cGy/MBq for total body, 0.21 ± 0.15 cGy/MBq for osteogenic cells, and 0.17 ± 0.15 cGy/MBq for kidneys. Conclusion:111In-DOTA-BC8 had a long retention time in liver, spleen, kidneys, and red marrow, and the highest absorbed doses were in spleen and liver. Few differences were observed by malignancy type. The exception was greater splenic uptake in the leukemia/MDS group than in the lymphoma or multiple myeloma group.

Total Synthesis of the Proposed Structure of Mycobactin J.

The total synthesis of the proposed structure of mycobactin J (MJ), a metabolite of Mycobacterium tuberculosis, is presented. The highlights of the synthesis include a careful control of the Z-stereochemistry of the unsaturated long chain fatty acid, a biomimetic construction of the oxazoline building block and the carriage of an unprotected phenol throughout the synthesis.

Synthesis of Fluoranthene Derivatives via Tandem Suzuki-Miyaura and Intramolecular C-H Arylation Reactions under Both Homogeneous and Heterogeneous Catalytic Conditions.

A catalytic method for the synthesis of substituted fluoranthenes that operates via tandem Suzuki-Miyaura and intramolecular C-H arylation reactions is reported. The overall reaction sequence works effectively with homogeneous catalysis using Pd(dppf)Cl2 as well as heterogeneous catalysis using reduced graphene oxide (rGO)-CuPd nanocatalysts with low catalyst loadings. High functional group tolerance is observed under both catalytic conditions where arylboronic acids and esters having electron-withdrawing and electron-donating substituents afforded fluoranthene products in good yields (up to 78%). Moreover, the rGO-CuPd nanocatalysts are demonstrated to be reusable by preserving almost 90% of their initial activity after the third cycle.

Preparation and evaluation of a new radiopharmaceutical for radiosynovectomy, 111Ag-labelled hydroxyapatite (HA) particles.

Many radionuclides, namely, 166Ho, 90Y, 165Dy, 32P, 198Au, 186Re, etc. have been used for radio-synovectomy. Silver-111 (T 1/2 7.45 d) can be produced in a nuclear reactor and is a potential therapeutic radionuclide decaying by beta(-) emission (92% E beta max=1.037MeV and 8% by beta(-) decay associated with emission of gamma-rays (E gamma=245.4keV, I gamma=1.33%; E gamma=342.1keV, I gamma=6.7%)). Because of the production feasibility and favourable nuclear properties, 111Ag may find use as a suitable radionuclide for radio-synovectomy. Hydroxyapatite (HA), Ca10(PO4)6(OH)2 is one of the preferred particulates for this application. In this work, [111Ag]Ag-HA particulates were successfully prepared with high-labelling yield ( approximately 97%) at various pH values. The radiochemical purity of the [111Ag]Ag-HA particles was 99.9%. Stability studies for 7 days showed that the [111Ag]Ag-HA particles retained their stability. gamma camera images at 15 min, 24h and 5 d after injection of the particles into rabbits revealed the retention of the activity in the synovial joints of the knee, thereby indicating excellent in vivo stability of [111Ag]Ag-HA particles. Therefore, [111Ag]Ag-HA particles would be a potential therapeutic agent in the management of arthritis.

A versatile technique for radiochemical separation of medically useful no-carrier-added (nca) radioarsenic from irradiated germanium oxide targets.

A method for the separation of no-carrier-added (nca) arsenic radionuclides from bulk amounts of irradiated germanium oxide (GeO2) target was developed in view of their potentialities in different biological and nuclear medicine applications. The beta- emitting 77As radionuclide, produced by the decay of 77Ge through the natGe(n,gamma)77Ge nuclear reaction, was used for standardization of the radiochemical separation procedure. The radiochemical separation was performed by precipitation followed by solvent extraction. About 99% post-irradiation recovery of the GeO2 target material, in a form suitable for reuse in future irradiation, was achieved. The developed method was suitable for the production of nca arsenic radionuclides either as trivalent or pentavalent arsenic in various vehicles which provided flexibility of formulations of different kinds of compound. The overall radiochemical yield for the complete separation of 77As was 90%. The separated nca 77As was of high radionuclidic purity and did not contain detectable amounts of the target material. This method can be adopted for the radiochemical separation of other different arsenic radionuclides produced from GeO2 through cyclotron as well as reactor irradiation.

Production and separation of no-carrier-added radioactive tracers of yttrium, strontium and rubidium from heavy-ion irradiated germanium target: applicability to the standardization of a separation technique for production of positron-emitting radionuclide 86Y.

Among various positron-emitting radionuclides, certain radioisotopes of Y, Sr and Rb have important applications in diagnostic and therapeutic nuclear medicine. In the present work, an attempt has been made to produce some of those radioisotopes by irradiating a natural Ge-target material with heavy-ion oxygen ((16)O(+6)) projectiles. An effective radiochemical separation scheme was developed to isolate Y, Sr and Rb radiotracers from the irradiated Ge-matrix in no-carrier-added form with a view to applying those radiotracers for standardization of a technique for the radiochemical separation of Y from natural Sr target. The standardized separation technique could be utilized for the production of the positron-emitting (86)Y from an enriched (86)Sr target irradiated at a medical cyclotron.