cyclotron production via (p,2n) on 100mo is the significant co-production of 99gtc. the preferential in-growth of this nuclide occurs due to the larger reaction cross-section pathway leading to the ground state, which is almost five times higher at the cross-section maximum in comparison with the metastable one at the same energy. depending on the time required to process the target material and recovery of 99mtc, the amount of 99mtc relative to 99gtc will continue to decrease, in turn reducing the specific activity of 99mtc available. it has been reported that ingrowth of 99gtc as well as the presence of other tc isotopes can negatively affect subsequent labelling and/or imaging; however, the use of high purity 100mo targets, specified proton beam energies, and appropriate time of use have shown to be sufficient for yielding 99mtc from a cyclotron comparable to that from a commercial generator. liquid metal molybdenum-containing targets have been proposed that would aid in streamlined processing, ensuring better production yields. a particular problem associated with the continued reuse of recycled, enriched 100mo targets is unavoidable transmutation of the target as other mo isotopes are generated during irradiation and cannot be easily removed post-processing. indirect routes of production of 99mo other particle accelerator-based isotope production techniques have been investigated. the supply disruptions of 99mo in the late 2000s and the ageing of the producing nuclear reactors forced the industry to look into alternative methods of production. the use of cyclotrons or electron accelerators to produce 99mo from 100mo via (p,pn) or (γ,n) reactions, respectively, has been further investigated. the (n,2n) reaction on 100mo yields a higher reaction cross-section for high energy neutrons than of (n,γ) on 98mo with thermal neutrons. in particular, this method requires accelerators that generate fast neutron spectrums, such as ones using d-t or other fusion-based reactions, or high energy spallation or knock out reactions. a disadvantage of these techniques is the necessity for enriched 100mo targets, which are significantly more expensive than natural isotopic targets and typically require recycling of the material, which can be costly, time-consuming, and arduous. technetium-99m generators main article: technetium-99m generator technetium-99m's short half-life of 6 hours makes storage impossible and would make transport very expensive. instead, its parent nuclide 99mo is supplied to hospitals after its extraction from the neutron-irradiated uranium targets and its purification in dedicated processing facilities. it is shipped by specialised radiopharmaceutical companies in the form of technetium-99m generators worldwide or directly distributed to the local market. the generators, colloquially known as moly cows, are devices designed to provide radiation shielding for transport and to minimize the extraction work done at the medical facility. a typical dose rate at 1 metre from the 99mtc generator is 20-50 μsv/h during transport. these generators' output declines with time and must be replaced weekly, since the half-life of 99mo is still only 66 hours. molybdenum-99 spontaneously decays to excited states of 99tc through beta decay. over 87% of the decays lead to the 142 kev excited state of 99mtc. a β− electron and a νe electron antineutrino are emitted in the process (99mo → 99mtc + β− + νe). the β− electrons are easily shielded for transport, and 99mtc generators are only minor radiation hazards, mostly due to secondary x-rays produced by the electrons (also known as bremsstrahlung). at the hospital, the 99mtc that forms through 99mo decay is chemically extracted from the technetium-99m generator. most commercial 99mo/99mtc generators use column chromatography, in which 99mo in the form of water-soluble molybdate, moo42− is adsorbed onto acid alumina (al2o3). when the 99mo decays, it forms pertechnetate tco4−, which, because of its single charge, is less tightly bound to the alumina. pulling normal saline solution through the column of immobilized 99moo42− elutes the soluble 99mtco4−, resulting in a saline solution containing the 99mtc as the dissolved sodium salt of the pertechnetate. one technetium-99m generator, holding only a few micrograms of 99mo, can potentially diagnose 10,000 patients because it will be producing 99mtc strongly for over a week. technetium scintigraphy of a neck of a graves' disease patient preparation technetium exits the generator in the form of the pertechnetate ion, tco4−. the oxidation state of tc in this compound is +7. this is directly suitable for medical applications only in bone scans (it is taken up by osteoblasts) and some thyroid scans (it is taken up in place of iodine by normal thyroid tissues). in other types of scans relying on 99mtc, a reducing agent is added to the pertechnetate solution to bring the oxidation state of the technecium down to +3 or +4. secondly, a ligand is added to form a coordination complex. the ligand is chosen to have an affinity for the specific organ to be targeted. for example, the exametazime complex of tc in oxidation state +3 is able to cross the blood–brain barrier and flow through the vessels in the brain for cerebral blood flow imaging. other ligands include sestamibi for myocardial perfusion imaging and mercapto acetyl triglycine for mag3 scan to measure renal function. medical uses in 1970, eckelman and richards presented the first "kit" containing all the ingredients required to release the 99mtc, "milked" from the generator, in the chemical form to be administered to the patient. technetium-99m is used in 20 million diagnostic nuclear medical procedures every year. approximately 85% of diagnostic imaging procedures in nuclear medicine use this isotope as radioactive tracer. klaus schwochau's book technetium lists 31 radiopharmaceuticals based on 99mtc for imaging and functional studies of the brain, myocardium, thyroid, lungs, liver, gallbladder, kidneys, skeleton, blood, and tumors. a more recent review is also available. depending on the procedure, the 99mtc is tagged (or bound to) a pharmaceutical that transports it to its required location. for example, when 99mtc is chemically bound to exametazime (hmpao), the drug is able to cross the blood–brain barrier and flow through the vessels in the brain for cerebral blood-flow imaging. this combination is also used for labeling white blood cells (99mtc labeled wbc) to visualize sites of infection. 99mtc sestamibi is used for myocardial perfusion imaging, which shows how well the blood flows through the heart. imaging to measure renal function is done by attaching 99mtc to mercaptoacetyl triglycine (mag3); this procedure is known as a mag3 scan. technetium-99m (tc-99m) can be readily detected in the body by medical equipment because it emits 140.5 kev gamma rays (these are about the same wavelength as emitted by conventional x-ray diagnostic equipment), and its half-life for gamma emission is six hours (meaning 94% of it decays to 99tc in 24 hours). besides, it emits no particle radiation, thus keeping radiation dosage low. its decay product, 99tc, has a relatively long half-life (211,000 years) and emits little radiation. the short physical half-life of 99mtc and its biological half-life of 1 day with its other favourable properties allows scanning procedures to collect data rapidly and keep total patient radiation exposure low. chemically, technetium is selectively concentrated in thyroid, salivary glands, and stomach and excluded from cerebrospinal fluid. combination with perchlorate abolishes its selectiveness. radiation side-effects diagnostic treatment involving technetium-99m will result in radiation exposure to technicians, patients, and passers-by. typical quantities of technetium administered for immunoscintigraphy tests, such as spect tests, range from 400 to 1,100 mbq (11 to 30 mci) (millicurie or mci; and mega-becquerel or mbq) for adults. these doses result in radiation exposures to the patient around 10 msv (1000 mrem), the equivalent of about 500 chest x-ray exposures. this level of radiation exposure is estimated by the linear no-threshold model to carry a 1 in 1000 lifetime risk of developing a solid cancer or leukemia in the patient. the risk is higher in younger patients, and lower in older ones. unlike a chest x-ray, the radiation source is inside the patient and will be carried around for a few days, exposing others to second-hand radiation. a spouse who stays constantly by the side of the patient through this time might receive one thousandth of patient's radiation dose this way. the short half-life of the isotope allows for scanning procedures that collect data rapidly. the isotope is also of a very low energy level for a gamma emitter. its ~140 kev of energy make it safer for use because of the substantially reduced ionization compared with other gamma emitters. the energy of gammas from 99mtc is about the same as the radiation from a commercial diagnostic x-ray machine, although the number of gammas emitted results in radiation doses more comparable to x-ray studies like computed tomography. technetium-99m has several features that make it safer than other possible isotopes. its gamma decay mode can be easily detected by a camera, allowing the use of smaller quantities. and because technetium-99m has a short half-life, its quick decay into the far less radioactive technetium-99 results in relatively low total radiation dose to the patient per unit of initial activity after administration, as compared with other radioisotopes. in the form administered in these medical tests (usually pertechnetate), technetium-99m and technetium-99 are eliminated from the body within a few days. 3-d scanning technique: spect main article: single-photon emission computed tomography single-photon emission computed tomography (spect) is a nuclear medicine imaging technique using gamma rays. it may be used with any gamma-emitting isotope, including 99mtc. in the use of technetium-99m, the radioisotope is administered to the patient and the escaping gamma rays are incident upon a moving gamma camera which computes and processes the image. to acquire spect images, the gamma camera is rotated around the patient. projections are acquired at defined points during the rotation, typically every three to six degrees. in most cases, a full 360° rotation is used to obtain an optimal reconstruction. the time taken to obtain each projection is also variable, but 15–20 seconds are typical. this gives a total scan time of 15–20 minutes. the technetium-99m radioisotope is used predominantly in bone and brain scans. for bone scans, the pertechnetate ion is used directly, as it is taken up by osteoblasts attempting to heal a skeletal injury, or (in some cases) as a reaction of these cells to a tumor (either primary or metastatic) in the bone. in brain scanning, 99mtc is attached to the chelating agent hmpao to create technetium (99mtc) exametazime, an agent which localizes in the brain according to region blood flow, making it useful for the detection of stroke and dementing illnesses that decrease regional brain flow and metabolism. most recently, technetium-99m scintigraphy has been combined with ct coregistration technology to produce spect/ct scans. these employ the same radioligands and have the same uses as spect scanning, but are able to provide even finer 3-d localization of high-uptake tissues, in cases where finer resolution is needed. an example is the sestamibi parathyroid scan which is performed using the 99mtc radioligand sestamibi, and can be done in either spect or spect/ct machines. bone scan the nuclear medicine technique commonly called the bone scan usually uses 99mtc. it is not to be confused with the "bone density scan", dexa, which is a low-exposure x-ray test measuring bone density to look for osteoporosis and other diseases where bones lose mass without rebuilding activity. the nuclear medicine technique is sensitive to areas of unusual bone rebuilding activity, since the radiopharmaceutical is taken up by osteoblast cells which build bone. the technique therefore is sensitive to fractures and bone reaction to bone tumors, including metastases. for a bone scan, the patient is injected with a small amount of radioactive material, such as 700–1,100 mbq (19–30 mci) of 99mtc-medronic acid and then scanned with a gamma camera. medronic acid is a phosphate derivative which can exchange places with bone phosphate in regions of active bone growth, so anchoring the radioisotope to that specific region. to view small lesions (less than 1 centimetre (0.39 in)) especially in the spine, the spect imaging technique may be required, but currently in the united states, most insurance companies require separate authorization for spect imaging. myocardial perfusion imaging main article: myocardial perfusion imaging myocardial perfusion imaging (mpi) is a form of functional cardiac imaging, used for the diagnosis of ischemic heart disease. the underlying principle is, under conditions of stress, diseased myocardium receives less blood flow than normal myocardium. mpi is one of several types of cardiac stress test. as a nuclear stress test,