Source: Health Products Regulatory Authority (IE) Revision Year: 2014 Publisher: Mallinckrodt Medical B.V., Westerduinweg 3, 1755 LE Petten, The Netherlands
Pharmacotherapeutic group: diagnostic radiopharmaceuticals, Technetium (99mTc) compounds
ATC code: V09GA01
At the chemical concentrations used for diagnostic examinations, technetium (99mTc) sestamibi solution does not appear to have any pharmacodynamic activity.
After reconstitution with sodium pertechnetate (99mTc), the following technetium (99mTc) sestamibi complex is formed:
[99mTc (MIBI)6] + Where: MIBI = 2-methoxyisobutylisonitrile
Technetium (99mTc) sestamibi from the blood is rapidly distributed into the tissue: 5 minutes after injection only about 8% of the injected dose remains in the blood pool. In physiological distribution, evident concentration of technetium (99mTc) sestamibi can be seen in vivo in several organs. In particular, normal tracer uptake is evident in the salivary glands, thyroid, myocardium, liver, gallbladder, small and large intestine, kidneys, bladder, choroid plexuses and skeletal muscles, occasionally in the nipples. Faint homogeneous uptake in the breast or axilla is normal.
Technetium (99mTc) sestamibi is a cationic complex which diffuses passively through the capillary and cell membrane. Within the cell it is localised in the mitochondria, where it is trapped, and retention is based on intact mitochondria, reflecting viable myocytes. After intravenous injection, it is distributed within the myocardium according to myocardial perfusion and viability. Myocardial uptake which is coronary flow dependent is 1.5% of the injected dose at stress and 1.2% of the injected dose at rest. Irreversibly damaged cells however do not take up technetium (99mTc) sestamibi. The myocardial extraction level is reduced by hypoxia. It has very little redistribution and so separate injections are required for stress and resting studies.
The tissue uptake of technetium (99mTc) sestamibi depends primarily on the vascularisation which is generally increased in tumor tissue. Technetium (99mTc) sestamibi accumulates in various neoplasms and most markedly in mitochondria. Its uptake is related to increased energy-dependent metabolism and cell proliferation. Its cellular accumulation is reduced when multidrug resistance proteins are overexpressed.
Technetium (99mTc) sestamibi localises in both parathyroid tissue and functioning thyroid tissue but usually washes out of normal thyroid tissue more rapidly than out of abnormal parathyroid tissue.
Elimination of technetium (99mTc) sestamibi occurs mostly through the kidneys and the hepatobiliary system. Activity of technetium (99mTc) sestamibi from the gallbladder appears in the intestine within one hour of injection. About 27% of the injected dose is cleared through renal elimination after 24 hours and approximately 33% of the injected dose is cleared through the faeces in 48 hours. The pharmacokinetics in patients with renal or hepatic impairment has not been characterised.
The biological myocardial half-life of technetium (99mTc) sestamibi is approximately 7 hours at rest and stress. The effective half-life (which includes biological and physical half-lives) is approximately 3 hours for the heart and approximately 30 minutes for the liver.
In acute intravenous toxicity studies in mice, rats and dogs, the lowest dose of the reconstituted Sestamibi kit that resulted in any deaths was 7 mg/kg (expressed as Cu (MIBI)4 BF4 content) in female rats. This corresponds to 500 times the maximal human dose (MHD) of 0.014 mg/kg for adults (70 kg). Neither rats nor dogs exhibited treatment related effects at reconstituted Sestamibi kit doses of 0.42 mg/kg (30 times MHD) and 0.07 mg/kg (5 times MHD) respectively for 28 days. At repeated dose administration, the first toxicity symptoms appeared during the administration of 150 times the daily dose during 28 days.
Extravasation administration in animals showed acute inflammation with oedema and haemorrhages at the injected site.
Studies on reproductive toxicity have not been conducted.
Cu (MIBI)4 BF4 showed no genotoxic activity in the Ames, CHO/HPRT and sister chromatid exchange tests. At cytotoxic concentrations, an increase in chromosome aberration was observed in the in vitro human lymphocyte assay. No genotoxic activity was observed in the in vivo mouse micronucleus test at 9 mg/kg.
Studies to assess the carcinogenic potential of the radiopharmaceutical kit have not been conducted.
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