astatine and Bone-Neoplasms

To summarise data with radium-223 dichloride (. Literature for this systematic review was identified using a PubMed search: ("targeted alpha therapy" or "targeted alpha particle therapy") or (213-bismuth or bismuth-213 or 213Bi) or (225-actinium or actinium-225 or 225Ac) or (211-astatine or astatine-211 or 211At) or (212-lead or lead-212 or 212Pb) or (227-thorium or thorium-227 or 227Th) or (223-radium or radium-223 or 223Ra or alpharadin) and (malignancy or cancer). Results were limited to English-language publications in humans, with the article type "clinical trial".. Forty-one publications were included (30 from the literature search and 11 from manual searches/reviews). In clinical trials in mCRPC,

Topics: Actinium; Astatine; Bismuth; Bone Neoplasms; Humans; Lead Radioisotopes; Male; Prostatic Neoplasms, Castration-Resistant; Quality of Life; Radioisotopes; Radium; Thorium

Bisphosphonates were synthesized for use as carriers for astatine and iodine radioisotopes to target bone neoplasms.. Radiohalogenated activated esters were coupled to the amino group in the side chain of the bisphosphonate. The bisphosphonate 3-amino-1-hydroxypropylidene bisphosphonate was combined with four different acylation agents: N-succinimidyl 3-[211At]astatobenzoate, N-succinimidyl 3-[131I]iodobenzoate, N-succinimidyl-5-[211At]astato-3-pyridinecarboxylate and N-succinimidyl-5-[131I]iodo-5-pyridinecarboxylate. The products, 3-[131I]iodobenzamide-N-3-hydroxypropylidene-3,3-bisphosphonate (IBPB), 3-[211At]astato-benzamide-N-3-hydroxypropylidene-3,3-bisphosphonat e (ABPB), 5-[131I]iodopyridine-3-amide-N-3-hydroxypropylidene-3,3-bisphospho nate (IPPB) and 5-[211At]astatopyridine-3-amide-N-3-hydroxypropylidene-3,3-bisphos phonate (APPB), were injected intravenously into Balb/c mice. MIRD and Monte Carlo methods were used on the basis of cumulated activity calculated from biodistribution data to estimate dose to organs and bone segments.. All 131I- and 211At-labeled analogs were strongly incorporated into osseous tissue and retained there at stable levels, while a rapid clearance from blood was observed. The bone uptake was found to be similar for 211At- and 131I-labeled bisphosphonate when compared in paired label experiments. Bone uptake and bone-to-tissue ratios were better for IBPB compared with IPPB, and ABPB compared with APPB. All four compounds appeared to be highly resistant to in vivo dehalogenation as indicated by low uptake of 131I/211At in the thyroid gland and stomach. According to dosimetric estimates, the bone surface-to-bone marrow ratio was three times higher with 211At than with 131I.. Both the beta-particle- and alpha-particle-emitting compounds showed high in vivo stability and excellent affinity for osseous tissue. Further preclinical evaluation is therefore warranted.

Topics: Animals; Astatine; Bone and Bones; Bone Neoplasms; Diphosphonates; Iodine Radioisotopes; Isotope Labeling; Male; Mice; Mice, Inbred BALB C; Time Factors; Tissue Distribution

The potential usefulness of alpha-particle radioimmunotherapy in the treatment of osteosarcoma was studied in vitro by using the monoclonal antibody TP-3 and cells of three human osteosarcoma cell lines (OHS, SAOS and KPDX) differing in antigen expression. Cell survival curves were established after treatment with (a) 211At-TP-3 of different specific activities, (b) 211At-labeled bovine serum albumin (BSA), (c) free 211At and (d) external-beam X rays. The three osteosarcoma cell lines showed similar survival curves, whether treated with external-beam X rays, 211At-BSA or free 211At. The D0's were lower for free 211At than for 211At-BSA. The survival curves for 211At-TP-3 treatment, on the other hand, differed significantly among the cell lines, suggesting that sensitivity to 211At-TP-3 treatment was governed by cellular properties other than sensitivity to external-beam X rays. The cellular property most important for sensitivity to 211At-TP-3 treatment was the antigen expression. Cell inactivation after 211At-TP-3 treatment increased substantially with increasing specific activity of the 211At-TP-3. At high specific activities, the cytotoxic effect of 211At-TP-3 was significantly higher than that of 211At-BSA. In conclusion, 211At-TP-3 has the potential to give clinically favorable therapeutic ratios in the treatment of osteosarcoma.

Topics: Antibodies, Monoclonal; Astatine; Bone Neoplasms; Cell Survival; Humans; Osteosarcoma; Radioimmunotherapy; Radiotherapy Dosage; Serum Albumin, Bovine; Tumor Cells, Cultured; X-Rays

Microcolonies were obtained by culturing cells of two human osteosarcoma lines (OHS and KPDX) and one human melanoma line (WIX-c) for either 24 or 72 h. The microcolonies were treated with either alpha-particle radiation emitted by the 211At-labelled monoclonal antibody (MAb) TP-3 or external beam X-rays. Survival of microcolonies was assayed by colony formation. Therapeutic gain factor (TGF) values were calculated for two survival levels, 50% and 20% microcolony regeneration (i.e. at least one cell in 50% or 20% of the colonies survived the treatments). The TGF values were affected by the specific activity of the 211At-MAb conjugate, the antigen expression of the cells and the size and growth pattern of the microcolonies. Treatment with 211At-TP-3 gave TGF values that varied from 1.3 +/- 0.4 to 4.5 +/- 0.7 (mean +/- s.e.). The antigen-rich OHS cell line had on average 1.6 times higher TGF than the antigen-poor KPDX cell line. The TGF increased significantly with colony size for the densely packed colonies of the KPDX cell line but not for the OHS cell line, which had colonies with cells growing in a more scattered pattern. Control experiments with the two non-specific 211At forms, free 211At and 211At-labelled bovine serum albumin, gave TGF values from 0.6 +/- 0.1 to 1.0 +/- 0.3. This study suggests that in vivo evaluation of 211At-MAbs using relevant tumour models is desirable.

Topics: Antibodies, Monoclonal; Astatine; Bone Neoplasms; Cell Division; Cell Line; Humans; Immunoglobulin G; Melanoma; Models, Biological; Osteosarcoma; Radioimmunotherapy; Tumor Cells, Cultured; X-Rays