Besilesomab
Besilesomab Uses, Dosage, Side Effects, Food Interaction and all others data.
Besilesomab is a mouse monoclonal antibody labelled with the radioactive isotope technetium-99m for determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis . Utilised only as a diagnostic agent, besilesomab is currently approved by the EMEA for marketing and use in various European countries like Italy, France, Germany, Spain, Portugal, Norway, Sweden, the Netherlands, and the United Kingdom .
In a study employing cryo-preserved human tissues using an indirect alkaline phosphatase anti-alkaline phosphatase technique, besilesomab antibody from hybridoma supernatants demonstrated staining to cytoplasmic, membranous, and interstitial areas of primary colon carcinoma tissue, to single granulocytic cells in normal human liver and lung and to a large proportion of granulocytic cells in normal human bone marrow but not to blood vessels or connective tissue . Additionally, the antibody also shows binding to the granulocytic cells of breast, kidney, parotid gland, pituitary, lymph nodes, and spleen tissues, as well as colonic, pancreatic, and some lung and breast carcinomas .
The purified besilesomab antibody and the prepared kit subsequently bound similarly to granulocytes in normal bone marrow, lung, liver, spleen, and colorectal carcinomas. Furthermore, the prepared kit also produced some staining in some connective tissue fibres in normal lung, some muscle fibres in normal colon, and in liver parenchymal cells . In general however, besilesomab does not bind significantly to blood vessels and connective tissue .
| Trade Name | Besilesomab |
| Generic | Besilesomab |
| Besilesomab Other Names | Besilesomab |
| Type | |
| Protein binding | Studies demonstrate that prepared kit besilesomab binds up to 97.45% and 96.58% of peripheral blood granulocytes in males and females respectively and less than 5% of other peripheral blood cells . Moreover, no significant binding of the antibody to other human peripheral blood cells like erythrocytes, platelets, lymphocytes, and monocytes was observed . As well, besilesomab demonstrates no cross-reactivity with human platelets . |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Besilesomab is a monoclonal antibody bound to technetium-99 used to find infection and inflammation in patients with suspected osteomyelitis.
Besilesomab is radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution. This solution is indicated in adults for scintigraphic imaging - in conjunction with other appropriate imaging modalities, when possible - in determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis . When utilized as such, this medicinal product is for diagnostic use only .
Besilesomab is also used to associated treatment for these conditions: Osteomyelitis of the peripheral bone
How Besilesomab works
Nonspecific cross-reacting antigens (NCA) is the name of a collection of highly glycosylated bacterial binding receptors expressed on human granulocytes and other tissues . In particular, these glycoprotein receptors are members of the immunoglobulin supergene family and are related structurally to carcinoembryonic antigen (CEA) . CEA is found naturally in the human body and its expression may be increased in both cancer and non-cancerous (benign) circumstances.
Besilesomab is subsequently a murine immunoglobulin monoclonal antibody of IgG1 isotype designed to recognise and bind specifically to NCA-95, or nonspecific cross-reacting antigen 95, an epitope found expressed on the cell membranes of granulocytes and granulocyte precursors .
When radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution, this radiolabelled medicine is injected into patients where the monoclonal antibody carries it to target CEA on target granulocytes . When large numbers of CEA expressing granulocytes gather to the site of an infection, the radioactive monoclonal antibodies will also accumulate at such sites, where it can be detected by diagnostic scanning . The resultant images show where the radioactive besilesomab has accumulated, locating areas affected by osteomyelitis, infection, or inflammation .
Furthermore, it is believed that the besilesomab accumulation is predominantly passive (via increased vascular permeability) and only partially active (via migration of human granulocytes carrying besilesomab to the infection/inflammation location) since only 10% to 20% of the injected radio-diagnostic agent binds in vivo to human circulating granulocytes . Specific binding of besilesomab to activated granulocytes that have already migrated to sites of infection/inflammation might be the primary part of the detection signal .
Toxicity
The most commonly reported adverse reaction associated with the use of besilesomab is the development of Human Anti-Mouse Antibodies (HAMA) after a single administration . Patients who have developed HAMA may potentially have a higher risk for hypersensitivity reactions. Screening for possible previous exposure to murine monoclonal antibodies and tests for the presence of HAMA in prospective patients should be made prior to administrating besilesomab . Moreover, because the incidence of developing HAMA appears to be dose related with besilesomab, the recommended dosage is restricted to no more than 250 micrograms of antibody per injection . Patients who are HAMA positive are consequently contraindicated from using besilesomab .
Hypersensitivity to besilesomab or to any other murine antibodies or to any of the excipients associated with the active besilesomab radio-diagnostic agent is subsequently a contraindication .
Some patients have also reported hypotension as a common adverse reaction .
As exposure to ionizing radiation is linked with cancer induction and a potential for developing hereditary defects, the use of radio-diagnostic besilesomab in pregnant women is considered a formal contraindication . If in doubt about a woman's potential pregnancy, alternative techniques to not using ionizing radiation should be considered and/or offered instead to the patient .
Moreover, although it is not known if besilesomab is excreted in human milk, the potential risk to a breast-fed child cannot be excluded . Furthermore, while consideration should be given to the possibility of perhaps delaying the administration of radionuclide agents until the mother has ceased breastfeeding or perhaps certainly choosing alternative radoopharmaceuticals with more appropriate secretion activity, if the use of besilesomab is absolutely necessary then the mother's breastfeeding should be stopped for three days and any expressed feeds during that time discarded . The time period of three days corresponds to 10 half-lives of technetium (Tc99m)(60 hours) . At that time, the remaining activity represents about 1/1000 of the initial activity in the body .
In general, close contact with infants and pregnant women should be restricted for patients who have been administered besilesomab during the first 12 hours after the injection .
Since besilesomab contains sorbitol, patients having any rare hereditary conditions of fructose intolerance should not be administered this medicine .
Because no sufficient data regarding the safety and efficacy of using besilesomab in children below the age of 18 years exists, the use of besilesomab in this patient population is not recommended .
Even though data regarding the repeated dosing of besilesomab is extremely limited, the use of besilesomab should only be used once in a patient's lifetime .
Other medicines that can inhibit inflammation or affect the hematopoietic system (like antibiotics and corticosteroids) can lead to false negative results. Such agents should therefore not be administered together with, or a short time before the injection of besilesomab .
Preclinical data obtained with the non-radioactive compound revealed no special hazard for humans based on conventional studies of safety pharmacology, single-dose and repeated dose toxicity, although antimurine antibodies were found in all dose groups (including controls) in a repeated-dose study in monkeys . Genotoxicity studies conducted to test for potentially genotoxic impurities were also negative. Long-term carcinogenicity studies and toxicity to reproduction have not yet been carried out .
Food Interaction
No interactions found.Volume of Distribution
In the besilesomab clinical trial Study 7D-101SZ-A, volumes of distribution were determined as approximately 4L - which was close to the plasma volume - in the central compartment, whether calculated from plasma radioactivity or from intact monoclonal antibody concentrations; the peripheral compartment was somewhat greater, at about 6L for both methods .
Elimination Route
As the diagnostic agent is administered intravenously, it is expected that the bioavailability is 100% .
Approximately six hours after injection, about 1.5% of the whole body radioactivity is detected in the liver while about 3.0% is found in the spleen . Observations twenty-four hours after injection demonstrate percentages of radioactivity of 1.6% in the liver and 2.3% in the spleen .
However, non pathological, unusual accumulations of the radioactive agent can be detected in the spleen (up to 6% of patients), in the bowel (up to 4% of patients), in the liver and bone marrow (up to 3% of patients), and in the thyroid and kidneys (up to 2% of patients) .
Half Life
Whole blood concentration-time radioactivity curves show a two-phase course, which can be subdivided into an early phase (0-2 h) and a late phase (5-24 h) . After correcting for the decay of radionuclide, the calculated half-life of the early phase is approximately 0.5 h while the late phase demonstrates a calculated half-life of 16 h . The terminal half-life in man is estimated to be approximately 23 h .
Clearance
Once administered into the body, prepared technetium (Tc99m) besilesomab can be metabolized into free amino acids, smaller radioactive fragments, or even free pertechnetate (Tc99m) . The besilesomab clinical study 7D-101SZ-A consequently reports separate estimated clearance rates of 0.322 L/h and 0.242 L/h that were calculated using monitored plasma radioactivity and from monitored intact monoclonal antibody concentrations, respectively .
Elimination Route
Measurement of radioactivity levels in urine shows that up to 14% of the administered activity is excreted via the bladder during the 24 h post-injection period. Low renal clearance activity (of 0.2 L/h for a glomerular filtration rate of approximately 7 L/h) also suggests that the kidney is not the primary route of besilesomab elimination .
Additionally, over 30 hours rat pharmacokinetic studies also similarly demonstrated that 31-34% of the radioactivity was excreted in the urine and only 7-13% in the faeces . The faecal elimination was observed primarily from the 17h time period onward .
Furthermore, while radioactivity associated with intact antibody tends to stay in the vascular compartment for a long time, metabolized radioactive fragments, small radio-metabolites, and free pertechnetate (Tc99m) clears quickly from blood and will accumulate in the kidneys and further in the urine . In all besilesomab studies to date, approximately 14% of the injected radioactivity was recovered in the urine, which was only collected for 24 hours after administration .
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