Technetium-99m is the most widely used radioisotope in diagnostic nuclear medicine. It is estimated that over 80% of the 25 million diagnostic nuclear medicine studies are carried out annually using Technetium-99m.

The basic principle of 99mTc labeling includes the reduction of 99mTc7+ (stable oxidation state) by reducing agents such as stannous chloride, stannous tartrate, sodium borohydride, HCL, ferrous sulfate, and dithionite.

Stannous chloride is most commonly used reducing agent in most preparations of the 99mTc-labeled compounds. Another method of reduction of 99mTc7+ involves electrolysis of a mixture of sodium pertechnetate and the compound to be labeled using anode of zirconium.

The parent radionuclide molybdenum-99 is prepared in abundance by the fission of uranium-235 in a nuclear reactor. Owing to its multiple oxidation states, 99mTc has a versatile chemistry, making it possible to produce a variety of complexes with specific desired characteristics.

The reasons for widespread use of 99mTc radionuclide in several radiopharmaceuticals are the favorable physical properties mentioned below

  • mode of decay with 140KeV energy
  • short half-life of 6 hours
  • low level of non-penetrating radiation and dosimetry for the patients
  • an efficient separation of high-specific-activity samples of radionuclide from its parent using 99Mo-99mTc generator (Figure 2).
Figure 2. The metastable isotope of Technetium decays after a half-life of 6.0 hours by a single 143 keV gamma emission
Figure 2. The metastable isotope of Technetium decays after a half-life of 6.0 hours by a single 143 keV gamma emission

Some radiopharmaceuticals developed using technetium-99m are enumerated below with short descriptions.

99mTc-Pertechnetate (99mTcO4 )

Pertechnetate is used for thyroid uptake studies, and in imaging of stomach, brain, Meckel’s diverticulum, first pass blood flow, first pass peripheral vascular, and salivary gland. It has wide clinical applications. 99mTcO4 is currently used as an alternative to radioactive 123I, although the latter is the most suitable agent. The use of 123I has been limited because it is cyclotron generated, cost ineffective, and not readily available.

99mTc-labeled Human Serum Albumin

Human serum albumin is available in the form of a kit. Labeling efficiency of 99mTc-HSA is greater than 90%. 99mTc-HSA with serial scanning is used for imaging the protein-losing enteropathy (PLE), blood pool, and lymphedema. It is used as cardiac blood pool imaging agent and acts as an adjunct in the diagnosis of pericardial effusion and ventricular aneurysm. It has also been used in placenta localization and lymphoscintigraphy to evaluate lymphatic drainage patterns of malignant melanoma.

99mT-Human Immunoglobulin

99mTc-HIGs are characterized by easy availability, simple preparation, and reproducibility. Increased permeability of the vascular endothelium accounts for their accumulation in intersitial spaces. 99mTc-Human immunoglobulin is used in infection and inflammation imaging studies. It has also been successfully used in radioimmunotherapy for carcinoma.

99mT-labeled Red Blood Cells

99mT-labeled RBC’s are used for gastrointestinal bleeding studies and cardiac blood pool imaging. 99mTc-labeled red blood cell scans (are recommended to confirm gastrointestinal (GI) bleeding. Ultratag RBC is a diagnostic kit for in vitro preparation of 99mT-labeled RBC. It is used for blood pool imaging, detection of sites of gastrointestinal bleeding, and cardiac first pass.

99mTc-methylene diphosphonate (MDP)

99mTc-MDP imaging is most frequently used diagnostic nuclear medicine procedure to obtain a bone scan (Figure 3). The bone scan obtained reflects mineral content, outlines physiological processes, such as, functional reaction of bone to traumatic, inflammatory, and neoplastic injury.

99mTc-MDP is superior to other bone scanning agents as they have rapid clearance from blood and soft tissues and has high-resolution for clinical skeletal scintigraphy. First diphosphonate used clinically was 1-hydroxyethylidene diphosphonate (HEDP), which was eventually replaced by MDP, as it had slow blood clearance and less skeletal affinity.

Figure 3. Bone scintigraphy using technethium-99m diphosphonate radiopharnaceutical
Figure 3. Bone scintigraphy using technethium-99m diphosphonate radiopharnaceutical


99mTc-PYP accumulates in bone. This probably occurs due to membrane breakdown and microcalcification in bone. Images become positive in 12 to 24 hours after acute myocardial infarction (MI) combined with 201Tl/PYP tomography employed to identify the infarct-related vessel in patients with acute MI.

99mTc-Sestamibi or Cardiolite

It is a coordination complex of technetium-99m with ligand methoxyisobutylisonitrile (MIBI). It is a lipophilic mono-ionic complex that accumulates in the myocardium by passive diffusion rather than being transported by Na+-K ATPase pump. A scan of a patient using MIBI is commonly known as a MIBI scan. 99mTc-Sestamibi (Figure 4) shows high affinity for the areas of high metabolism, as is commonly seen in tumor cells.

Figure 4. 3D representation of 99mTc-Sestamibi
Figure 4. 3D representation of 99mTc-Sestamibi

It is mainly used for the detection of myocardial perfusion abnormalities (infarcts and ischemia) hyperparathyroidism and tumor. The mechanism of uptake of 99mTc-sestamibi by the cells is not entirely clear, but it seems to be related to concentration of mitochondria inside the cells and electrochemical gradient across the cell membrane. Malignant tumor cells maintain higher mitochondrial and plasma transmembrane potentials that cause increased accumulation of MIBI, making it a suitable radiotracer.

99mTc-Tebroxime or Cardiotec

99mTc-Tebroxime is a lipophilic agent. First t1/2 of 99mTc-Teboroxime is 0.79 minute and second t1/2 is 155 minutes. It is myocardial perfusion agent used to distinguish normal and abnormal myocardium. It is valuable in non-invasive assessment of relative coronary flow reserve to detect coronary artery stenosis and has a distinct advantage over 201Tl.


99mTc-tetrofosmin (Figure 5) is a hydrophobic cationic compound, which was designed originally as a radiopharmaceutical for myocardial perfusion imaging. 99mTc-Tetrafosmin is sold under brand name Myoview (GE healthcare).

Figure 5. Molecular structure of 99mTc-Tetrafosmin
Figure 5. Molecular structure of 99mTc-Tetrafosmin

It is a lipophilic perfusion radiotracer that accumulates in myocardium in proportion to blood flow. Its uptake in myocardium is due to a membrane potential-driven mechanism.

99mTc-tetrofosmin is formed by the process of chelation of 99mTc with two 1,2-bis [di-(2-ethoxyethyl) phosphino] ethane ligands. It is used for axillary lymph node staging in breast cancer, detecting myocardial ischemia, myocardial infarction and tumor. It is an extremely stable complex and offers possible formulation advantages over other 99mTc complexes. For example, room temperature reconstitution from a lyophilized kit.

99mTc-Mercaptoacetylglycylglycylglycine (MAG3)

Fritzberg et al introduced 99mTc-MAG3 in 1986. It is primarily used for the evaluation of renal function. It is widely used to study renal scintigraphy, diuresis renography, captopril augmented renography, and renal transplant. It is used as an alternative to radiohippurate for the evaluation of nephrological disorders, such as renovascular hypertension.

99mTc-labeled Ciprofloxacin (Infecton)

99mTc-ciprofloxacin is biologically active radiopharmaceutical for the diagnosis of various infections. It is used for the diagnosis of deep-seated bacterial infections, such as intra-abdominal abscesses, endocarditis, and osteomyelitis. 99mTc-ciprofloxacin (Infecton) is useful radiotracer for detection of infectious foci in bones, joints, and vertebral infections.

99mTc-labeled Isoniazid and 99mTc-Labeled Ethambutol

99mTc-INH and 99mTc-EMB has been successfully used for the diagnosis of sensitive as well as resistant tuberculosis in patients. These radiotracers are used to target Mycobacterium tuberculosis as these drugs interact specifically with mycolic acid, an important constituent of mycobacterial cell wall. Bactericidal (INH) and bacteriostatic (EMB) drugs can be used with an aim to prevent the selection of resistant forms. Therapeutic efficacy of the 99mTc-INH (Figure 6) and 99mTc-EMB was exploited for diagnostic purpose.

Figure 6. Scintigram representing accumulation of 99mTc-INH in patient’s ankle with bone TB
Figure 6. Scintigram representing accumulation of 99mTc-INH in patient’s ankle with bone TB

99mTc-Hexamethyl propylene amine oxime (HMPAO) or Ceretec

99mTc-HMPAO is a lipophilic compound with the ability to cross the BBB and to accumulate in the brain. It is also called 99mTc-exametazime.

99mTc-HMPAO (Figure 7) is retained by tissues as it gets converted to hydrophilic forms from lipophilic form. It is a well-established isotope used for detection of regional cerebral blood flow, cerebrovascular disease, cerebral embolism, brain perfusion, and leukocyte labeling. 99mTc-HMPAO encapsulating VIP sterically stabilized liposomes can be successfully used for targeted imaging of the breast cancer.

Figure 7. Molecular structure of Ceretec
Figure 7. Molecular structure of Ceretec

99mTc-Pentetate (DTPA)

The kits of DTPA are available commercially. DTPA is primarily used to monitor renal flow, to measure glomerular filtration rate (GFR), and to prepare aerosol for lung ventilation studies.