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Similarly plavix 75mg with amex, it may also happen to alcoholics and people with other types of very monotonous diets order plavix with mastercard. The different deciency syndromes of vitamin B overlap and are sometimes very difcult to dis- tinguish from one another order plavix discount. A recent example is the Cuban neuropathy in the mid-1990s order 75 mg plavix fast delivery, in which over 50 000 people suffered from a gait and visual disturbance, technically a polyneuropathy (8, 9). It is now known that the population that experienced the epidemic had an extreme diet (tea with sugar as the main source of energy; which is likely to generate a vitamin B deciency) and the epidemic stopped as soon as universal distribution was made of tablets with vitamin B complex. This led the scientists to conclude that it was a vitamin B complex deciency, without being able to distinguish the vitamins from each other. From a public health perspective, therefore, the B vitamins may as well be treated together, the only exceptions being vitamin B12 and folate. Beri-beri is one form of vitamin B1 deciency, and the main symptom is a polyneuropathy in the legs (10). In severe cases, one can suffer from cardiovascular complica- tions, tremor, and gait and visual disturbances. An acute form of the syndrome seen in alcoholics is Wernicke s encephalopathy (discussed in the section on alcohol). It is characterized by a seri- ous confusion, unsteadiness and eye movement disorders. It can be rapidly reversed if correctly diagnosed and immediately treated with high-dose thiamine. Deciency of niacin leads to pellagra, an Italian word for rough skin, which was common in Italy and Spain in the 19th century when large populations were sustained on a maize diet. Neuropsychiatric disorders including seizures, migraine, chronic pain and depression have been linked to vitamin B6 deciency (11). Some studies have suggested that neurological development in newborns could be improved by supplementation in pregnancy, but this is still a hypothesis (12). Vitamin B6 deciency may occur especially during intake of some drugs which antagonize with the vitamin (i. Folate (or folic acid) plays an important role for rapidly dividing cells such as the blood cells, and a folate deciency causes a special type of anaemia called megaloblastic anaemia which is reversible when folate is given. Folate supplementation for women at the time of conception protects against neural tube defects (13). Supplementation of folate in wheat our is therefore common in Europe and North America, with the objective of reducing the risk of neural tube defect (14 16). In Canada, Chile and the United States, mandatory fortication of our substantially improved folate and homocysteine status, and neural tube defect rates fell by between 31% and 78% (17 ). Thus additional creative public health approaches need to be developed to prevent neural tube defects and improve the folate status of the general population. The vitamin B12 or cobalamine is like folate important in the formation of blood cells, particularly the red blood cells. Vitamin B12 is different from the other B vitamins because it needs an intrinsic factor produced by the gut in order to be absorbed. This means that people with gut disorders and also elderly people may experience vitamin B12 deciency. Vitamin B12 deciency also causes a megaloblastic anaemia which is reversible when vitamin B12 is given. What is worse is an insidious irreversible damage to the central and periph- eral nervous systems. In a severe form it may also cause a psychiatric disorder with irritability, aggressiveness and confusion. It has been suggested that vitamin B12 deciency might contribute to age-related cognitive impairment; low serum B12 concentrations are found in more than 10% of older people (18) but so far there is insufcient proof of benecial effects of supplementation. The most serious problem with vitamin B12 deciency still seems to be the irreversible progressive myeloneuropathy, which is difcult to diagnose. Iodine deciency disorders Iodine deciency does not cause one single disease, but many disturbances in the body. These are denoted by the term iodine deciency disorders: their effects range from increased mortality of fetuses and children, constrained mental development in its worst form, cretinism to impaired school performance and socioeconomic development, as detailed in Table 3. Goitre indicated by a swelling of the thyroid gland is present in 740 million people, and some 300 million suffer from lowered mental ability as a result of a lack of iodine. At least 120 000 children every year are born cretins mentally re- tarded, physically stunted, deaf-mute or paralysed as a result of iodine deciency. At that time, the scale and severity of the iodine problem was only just being realized. Since then, several surveys have shown even more severe damage than was estimated from this deciency in many regions of the world. Work to eliminate iodine deciency disorders has made enormous progress and is becoming a success story in the prevention of a nutritional deciency. The main intervention strategy for control of iodine deciency disorders is universal salt io- dization. Over the last decade, extraordinary progress has been made in increasing the number of people consuming iodized salt. Now, more than two thirds of households living in countries affected by iodine deciency disorders consume iodized salt. Because of active programmes of salt fortication, iodine deciency disorders are rapidly declining in the world. In 1990, 40 million children were born with mental impairment attributable to iodine deciency and 120 000 cretins were born, which was substantially more than just seven years later. A challenge is to enforce the legislation that has been passed in all but seven of the countries of the world with a recognized iodine-deciency public health problem. All the salt producers, from large industries to small-scale producers, need to be encouraged to use the more expensive procedure to fortify their salt production, and the consumers also need to be informed. Quality control and monitoring of the impact of the procedures are other continuing tasks related to the world s most widespread preventable cause of mental impairment (20). Iron deciency seems to be the only micronutrient deciency that high income and low income countries have in common. Iron deciency anaemia depresses human productivity by tiredness, breathlessness, decreased immune function and impaired learning in children. The effect of iron deciency on learning is difcult to study because iron deciency is also closely related to poverty and socioeconomic disadvantage. The indirect productivity effects of improved iron status are on cognitive ability and achievement, through impact on mental and motor skills in infants and on cognition, learning and behaviour in children and adolescents. An early severe chronic iron deciency leads to poorer overall cognitive functioning and lower school achievements (21, 22). The most affected populations are children in the pre-school years and pregnant women in low and middle income countries. A low dietary intake of iron and the inuence of factors affecting absorption also contribute to iron deciency. About 40% of the women in low and middle income countries and up to 15% in high income countries suffer from anaemia. Better nutrition, iron supplementation or fortication, child spacing and the prevention and treatment of malaria and hookworms can all prevent iron deciency. Correction of iron deciency anaemia is cheap, but a functioning health service is needed to promote the measures among the most vulnerable groups. There is, however, some evidence to suggest that iron supplementation at levels recommended for otherwise healthy chil- dren carries the risk of increased severity of infectious disease in the presence of malaria and/or undernutrition. It is therefore advised that iron and folic acid supplementation be targeted to those who are anaemic and at risk of iron deciency. They should receive concurrent protection from malaria and other infectious diseases through prevention and effective case management (25). In addition, zinc supplementa- tion of young children in low income countries improves their neurophysiological performance (26), also in combination with iron supplements (27). Selenium deciency Selenium deciency has been linked to adverse mood states (29). Selenium supplementation together with other vitamins has been found benecial in the treatment of mood lability (30). Generally, the scientic information about selenium and neurological disorders remains scarce. There are, however, still a number of obscure neurological disorders occurring in localized epidemics or endemic foci in tropical countries. Most of these syndromes consist of various combinations of peripheral polyneuropathy and signs of spinal cord involvement.

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Subepithelial deposits can pertension generic plavix 75 mg with amex, recurrent or persistent proteinuria and lead to a variable degree of proteinuria discount 75 mg plavix with visa. Mild facial oedema and hypertension are glomerular disease may have been membranoprolif- variably present discount 75 mg plavix visa. All the glomeruli demonstrate endothelial cheap plavix 75mg with mastercard, epithelial and mesangial cell proliferation, together with neu- trophils. Focalsegmentalproliferativeglomerulonephritisischar- acterised by cellular proliferation affecting only one Complications segment of the glomerulus and occurring in only a pro- Severe acute renal failure, rapidly progressive glomeru- portion of all glomeruli. Aetiology This histological pattern is caused by: Investigations r Primary glomerular diseases such as IgA nephropathy Renal biopsy is required to make a denitive diagnosis (also called mesangial IgA disease or Berger s disease) but may not always be necessary. Chronic renal failure may also There are immune complexes deposited in the glomeru- occur. Thereactiontothisislocalisedinammationand mesangialproliferation,causingreductionofrenalblood Investigations ow, leading to haematuria and in some acute cases, Serum IgA levels are high in 50%. Whereas IgA nephropathy tends to fol- icant proteinuria the course is usually benign and the low a slower, more benign course, a more orid form diagnosis is made clinically. Those with deterioration in occurs in Goodpasture s disease and the systemic causes renal function or with persistent signicant proteinuria in particular. IgAnephropathy (also called mesangial IgA disease or r Hypertension should be treated. The commonest glomerulonephritis in the developed r Corticosteroidsareonlyusedinselectedpatients,such world. Schonlein Purpura, cirrhosis, coeliac disease and der- r More aggressive immunosuppression may benet matitis herpetiformis. There is a weak association with some patients, such as those with crescentic disease. Clinical features Proteinuria, renal impairment and histological evidence One third of patients present with recurrent macro- of scarring, tubular atrophy and capillary loop deposits scopic haematuria during or after upper respiratory signify a worse prognosis. Approximately a third de- tract infections, one third have persistent microscopic veloprenalimpairment,andathirdreachend-stagerenal haematuria and/or persistent mild proteinuria. M > F r Pulmonary function tests may be performed to look for increased transfer factor (evidence of alveolar Aetiology/pathophysiology haemorrhage). Crescents form as a result of ep- are used to switch off the production of antibody. The decision to treat these The usual presentation is of acute renal failure with patients if they have no evidence of pulmonary haem- oliguria, an active urine sediment with dysmorphic orrhage or other vasculitis with aggressive therapy is redblood cells, red cell casts and proteinuria. Patient survival and long-term renal function correlate well with the degree of renal impairment at presenta- Macroscopy/microscopy tion. Early diagnosis and treatment is Immunouorescence demonstrates linear IgG and C3 the key to reducing morbidity and mortality. There is no evidence of an Patientsusuallypresentwithhaematuriaand/orprotein- immune complex process. In severe cases lial cells is believed to cause a reduction in the xed patientsmaypresentwithnephroticsyndrome,nephritic negative charge on the glomerular capillary wall, which syndrome or a mixed picture. Features of any underlying permits protein (particularly albumin) to cross into the condition may also be present. Resultant hypoalbuminaemia causes a re- duced blood oncotic pressure and hence oedema. Underlying causes should be looked for, partic- Clinical features ularly treatable infections, malignancies and cryoglobu- Patients present with gradual development of swelling linaemia. Renal function is usually Treatment of any underlying cause may lead to partial normal in uncomplicated cases. In those without nephrotic syn- drome, conservative management is probably indicated, Macroscopy/microscopy as the prognosis is good. In those with nephrotic-range Electron microscopy reveals fusion of the foot processes proteinuria, specic treatments such as steroids and an- ofthepodocytes,thisisdiagnosticifthelightmicroscopy tiplatelet agents may be tried with very variable benet. Cyclophosphamide, cyclosporine and other drugs have also been used to induce remission in Pathophysiology steroid-resistant cases, or to reduce the steroid dose The mechanism is unknown. Because the immune deposits are subepithe- Repeat renal biopsy may demonstrate another condition lial there is usually no marked inammatory response. Over many years, there is increase in mesangial matrix caus- Membranous glomerulonephritis ing hyalinization of glomeruli and loss of nephrons. Denition Clinical features This is the one of the two most common causes of Patients may present with asymptomatic proteinuria, nephrotic syndrome in non-diabetic adults (together or (in most cases) nephrotic syndrome. The idiopathic form causes 20% usually with mild to moderate mesangial proliferation. Silver stains classically show spikes where basement membrane has grown between subepithelial deposits. Alternatively large plasma proteins may leak through the capillary wall, accumulate in the subendothelial space and compress the capillary Prognosis lumen. Some patients develop a rapidly progressive course loss of the function of that nephron. These may develop later in the course of drome in adults and the second most common cause the illness. Incidence/prevalence Causes 20% of cases of nephrotic syndrome in adults Macroscopy/microscopy and children. Increase in the mesangial matrix in glomeruli in a focal segmental pattern, with collapse of the adjacent capillary loop. It is thought to be part rst, the disease may be missed on renal biopsy (and of a physiological response to glomerular hyperltra- hence a diagnosis of minimal change disease made). Steroid resistant cases action to the drug, with lymphocytes and eosinophils may respond to ciclosporin, and steroid-dependent inltrating the interstitium causing tissue oedema. The cases may benet from the addition of ciclosporin or tubular epithelium undergoes acute necrosis. High Patients with marked proteinuria, tubular atrophy, in- dose steroids may be given. Chronic renal failure may progress to end-stage renal disease and re- Acute Chronic quire renal replacement therapy. See also Renal Tubu- depletion, polyuria and immunodeciency secondary lar Acidosis (see below). Water and r Phosphate transport defects: There are several types, anions such as aminoacids follow sodium. Osmotic di- usually X-linked, although occasional sporadic inher- uretics and carbonic anhydrase inhibitors act at this site. Treatment is with oral phosphate supple- condition characterised by glycosuria with normal ments with vitamin D or 1,25 dihydroxyvitamin D blood glucose. Thick ascending loop of Henle: Sodium is pumped Glycosuria is a normal response during pregnancy. The most important single defect is cystinuria, an concentration gradient within the medulla of the kid- autosomal recessive condition which predisposes to ney, which draws water out of the collecting duct and urinary stone formation (see page 270). Loop diuretics such as with high uid intake and alkali ingestion, because the furosemide act from within the lumen of the ascending cystine is more soluble in alkaline conditions. Even when bicarbonate levels fall to as low This results in a similar syndrome of sodium loss, de- as 10 mmol/L or below, the urine remains relatively hydration and hypercalciuria as Bartter type I; how- alkaline (pH 5. If untreated, persistent metabolic ever, hypokalaemia only occurs after treatment with acidosis leads to increased mobilisation of calcium sodium supplements. Once 3 collecting duct resulting in a hypokalaemic metabolic plasma bicarbonate levels fall to about 12 16 mmol/L, alkalosis. This The main problems occur due to the loss of other is under the inuence of aldosterone which increases substances such as amino acids and phosphate. Spironolactone 2istreated with bicarbonate, thiazide diuretic and and amiloride affect this exchange and hence increase potassium bicarbonate or potassium-sparing diuret- urinary water and sodium loss. Fanconi syndrome is treated with large doses of diuretics, these cause potassium reabsorption and are vitamin D. This results in excessive water loss deciency causes hyperkalaemia, which is associated in the urine.

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Interestingly order 75mg plavix fast delivery, it has also been shown that exposure to cat or dog allergen early in life may actually be protective against later development of asthma order plavix 75 mg on-line. Certain bacterial infections including Chlamydia pneumoniae and Mycoplasma pneumoniae order cheapest plavix and plavix, as well as a number of viral infections purchase 75mg plavix mastercard, can stimulate local inflammatory reactions, and may be associated with asthma. Low or high birth weight, prematurity, and obesity have been shown to increase the risk of asthma. Just as with coronary artery disease, consumption of oily fish (salmon, tuna, shark) rich in omega-3 fats may be protective. Occupational asthma is airflow limitation and/or airway hyperresponsiveness caused by exposure to a specific agent or conditions in a particular work environment. Several cohort studies have suggested that work-related exposure to machining fluid, chemicals, laboratory animals, flour and latex may be associated with new-onset asthma. In contrast to work-related asthma, work- aggravated asthma is defined by preexisting asthma that is made worse or exacerbated by the work environment. All of these illnesses have in common provocability (reaction to airborne irritants, allergens, temperature/humidity and exercise), at least partially reversible airways obstruction in response to asthma medications (see below) and may rarely progress to irreversible lower airways obstructive disease (airway remodeling). Microscopically, there is a patchy loss of the epithelium or cellular layer covering the airway, leaving airway nerves exposed. There is accumulation of inflammatory cells, including eosinophils, which can release their contents and cause further inflammation. Enlargement of airway smooth muscle, increased number and size of bronchial blood vessels, and an accumulation of abnormal mucus in the airways all contribute to worsening airflow obstruction. Persistent inflammation may lead to a change in the structure of the airway due to the development of fibrosis (scar-like tissue) beneath the cellular layer covering of the bronchus. Goblet (mucus) cell metaplasia, subepithelial fbrosis, and eosinophilic infltration of the submucosa are shown. Cough can occur in association with these symptoms or be the only symptom, a condition called cough-variant asthma. Physical findings on examination include tachypnea (increased respiratory rate), wheezing, and a prolonged time-phase for expiration. When the presentation is more severe, decreased breath sounds, excessive use of respiratory muscles and rarely even cyanosis (low oxygen levels causing bluish discoloration of skin and mucous membranes) can be found. Family history, symptoms, and physical examination may suggest the diagnosis of asthma. Lung function testing may confirm the diagnosis and exclude other causes of these symptoms. Spirometry is a test most commonly used to evaluate the two main characteristic features of asthma: airflow obstruction, which is at least partially reversible, and airway hyperresponsiveness. During spirometry, patients are asked to forcibly exhale after taking a full breath in. After consistent measurements are obtained, a bronchodilator is administered and the testing is repeated to assess change. This method however is more effort dependent and less reproducible than spirometry. Bronchoprovocative tests measuring airway hyperresponsiveness can be done if baseline spirometry is normal or near-normal but the patient has symptoms suggestive of asthma. A negative methacholine challenge test virtually excludes asthma due to its high sensitivity. Several other tests are often done to evaluate a patient with suspected asthma, but are not diagnostic. The presence of positive skin tests may help the patient avoid specific allergens that can trigger or worsen asthma. Sputum analysis and chest x-rays are generally non-specific in asthma, but are more useful in excluding other disease processes. Oxygenation is usually not a problem during most asthma attacks but measurement of oxygen saturation is helpful in severe exacerbations. A new measure of asthma severity is the amount of exhaled nitric oxide, a marker of inflammation. Patients with intermittent asthma are treated with short-acting bronchodilators, used when needed. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma, Summary Report, 2007. To achieve these goals, asthma management must include patient education, monitoring, and avoidance of known triggers. Quick-relief medications are taken to promptly reverse airflow obstruction and relieve symptoms. Long-term control medications are taken daily to maintain control of persistent asthma with the goal of reducing the number of attacks and their severity. Generally, the treatment is based on the severity of asthma (refer back to Table 2-4. The action begins within five minutes of use and lasts as long as four hours, and may require re-dosing. Other agents in this class are marketed in the United States under the trade names Ventolin, Proventil, Proair and Maxair. Long-acting preparations of beta-agonists are also available but should never be used as quick-relief medications and should never be used without an inhaled corticosteroid. Anticholinergics Anticholinergics, such as ipratropium bromide (marketed as Atrovent ), also promote smooth muscle relaxation, though beta-agonists are more effective bronchodilators in the asthmatic population. In general, these agents are used when there is intolerance to beta-agonists, but in certain cases they may be used in combination (albuterol plus ipratropium bromide, marketed as Combivent ). A long-acting anticholinergic medication, tiotropium (marketed as Spiriva ), is currently available but not indicated for asthma at this time. Numerous studies have shown that inhaled steroids reduce daily asthma symptoms, reduce the severity and frequency of asthma exacerbations, reduce the need for bronchodilator therapy, and improve lung function. Most importantly, regular use of inhaled steroids is associated with reduced asthma mortality. Common side-effects are oral thrush (fungal infection), change of voice, and cough. It is extremely unusual for inhaled corticosteroids to cause the side-effects associated with oral corticosteroids (see below). They are also available in combination with long acting beta-agonists and marketed under the trade names Advair and Symbicort. Both have significantly longer half lives than albuterol, thereby requiring dosing only every 12 hours. One large study raised concern regarding asthma mortality and use of long-acting beta-agonists as monotherapy. It remains unclear if this was a reflection of a drug side-effect or underlying asthma disease severity. Until this is known, these agents should always be used in combination with inhaled steroids This combination is indicated in those patients who have moderate or severe persistent asthma. Single inhalers containing both a long acting beta-agonist and an inhaled corticosteroid (marketed as Advair and Symbicort ) are available to promote compliance and to help prevent the use of these agents as monotherapy. Leukotriene antagonists block leukotrienes which are substances released from inflammatory cells and that cause bronchoconstriction. This class of medication, of which the most commonly used is montelukast (marketed as Singulair ) is available in pill form, and is usually taken at nighttime. They may play a role in treating patients with environmental allergies as well as aspirin- sensitive asthma. Mast Cell Stabilizers Mast cell stabilizers include cromolyn (marketed as Intal ) and nedocromil. Overall, the role of this class of medication in the treatment of adult asthmatics is considered limited. Methyxanthines Methylxanthines, such as theophyline (marketed as Theodur or Unidur ), are one of the oldest classes of asthma medication. It is not currently recommended as a first line medication, but can be considered as an add-on therapy to inhaled steroids.

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Radio- Half-life Daughters Half-life Cumulative E mean Range nuclide /decay (MeV) (m) Tb-149 4 order genuine plavix on line. Very short-lived daughters The drawback of the short half-life of 212Bi might (ms to ms) will decay locally before difusing very far be overcome when using the beta-decaying 212Pb as but longer-lived daughters (seconds to hours) might an in vivo generator buy plavix online from canada. Strategies to control and limit the release of Another longer-lived alpha emitter is 211At purchase plavix online pills. The daughter nuclides by scavengers or by incorporating difculty of its application resides more in its (bio-) the primary nuclide into lipids or carbon nanotubes chemistry generic 75 mg plavix with mastercard. The single alpha emitters do not have the prob- For therapeutic applications it is essential to ensure lem of daughter activities but are mainly short-lived. Terefore they have with trace quantities supported by computational mainly been used in combination with peptides that chemistry [Cha11]. Interestingly, the ionisation have sufciently quick uptake and with antibodies potential of astatine, one of the fundamental atomic seeking blood cancer cells. This by intra-tumoral implantation of specially prepared value can now serve as experimental benchmark to radioactive sources of relatively low activity, which support in silico design of astatine compounds for continually release short lived -emitting atoms nuclear medicine applications. As these atoms spread inside 211At-labelled antibodies have been used clinically the tumour by the combined efects of interstitial for treatment of brain cancer [Zal08]. Phase I trials difusion and vascular convection, they deliver a for treatment of prostate cancer micrometastases well-localised high radiation dose through their and of neuroblastoma with 211At labelled antibodies -decays, leading to massive tumour cell destruction. Since the -emitters begin their journey in the intra- Preclinically 211At-labelled antibodies have been tumoral cellular space and no molecular targeting used against acute myeloid leukaemia as well as can- mechanism is involved, their subsequent distribu- cers of the ovary and intestine. Cell destruction must extend continuously lead with the well-known chemical properties of a over a few millimetres about the source (two orders lanthanide. If this sus beta radiation (of 161Tb or chemically similar is the case, tumours may be treated by deploying a 177Lu). First preclinical studies have been reported fnite number of sources at a typical spacing of a 109 [Bey04,Mue12] but so far this interesting isotope few millimetres, similar to brachytherapy. Tus, the source consists of par- cally against breast and ovarian cancer and 230U has ent -emitting atoms embedded closely below its been proposed as another long-lived alpha emitter. To implement cell lines in mice and human derived cell lines in the idea, one uses the -decay chain beginning with nude mice. The source a thin promising results in the treatment of malignancies conducting wire (0. Once inside the tumour and over a period which exist in solid tumours (such as the elevated determined by the 224Ra half-life (3. While some of these barriers may be with no chemical interactions, occasionally entering partially overcome by direct intra-tumoral injection and leaving the porous network of tumoral blood of the targeting molecules, this option has yet to be vessels. Nobel prize in physiology and medicine in 2001 is largely based on radioassay techniques employing 1. The logical progression of the increase in selectivity from beta to alpha emitters would be Auger elec- tron emitters. Low-energy Auger electrons have a very short range of nm to mm and high linear energy transfer. If they are brought close to the cell s nucleus they may be extremely efective in inducing double strand breaks but they are rather harmless while outside of non-targeted cells. Tus the selectivity of very targeted delivery agents that will specifcally internalise into cancer cells is max- imised. Auger electron therapy, a long-term project In 1927 (briefy afer the discovery of Auger electrons) the radiation therapy pioneers Claudius Regaud and Antoine Lacassagne concluded: The ideal agent for cancer therapy would consist of heavy elements capable of emit- ting radiations of molecular dimensions, which could be administered to the organism and selec- tively fxed in the protoplasm of cells one seeks to destroy. While this is perhaps not impossible to achieve, the attempts so far have been unsuc- cessful. For a comparison of efective specifc activity the ratio of activity over diferent methods one has to consider not only the the mass of all interfering elements. A given amount of pure radioisotopes should be avoided to avoid unneces- shorter-lived isotopes has obviously a higher activ- sary dose to the patient and extra burden on facility ity than the same amount of longer-lived isotopes. However, for practical purposes one has to con- sider that the radioisotopes are ofen diluted by 2. For meta- slightly neutron-rich isotopes that decay by beta- bolic targeting of thyroid or bone metastases very minus emission. Instead the clinical relevance that could in principle be pro- radioisotope is ofen diluted on purpose to avoid an duced by neutron capture is 64Cu. If other reactions (such as destruction of the tar- On the other hand for tumour cell types that get or product by nuclear reactions) do not interfere have only few selective sites (peptide receptors signifcantly, then the specifc activity achievable by or antigens respectively) it is crucial to use radio- a one-step transmutation reaction is given by: isotopes with very high specifc activity. Only the same element may be interfering but also those 60Co, 153Sm, 169Yb and 177Lu can be produced with appreciable specifc activity (R > 0. To optimise specifc activity ofen the target material is enriched in the useful target isotope and depleted in other stable isotopes that do not contrib- ute to the production of the desired radioisotope. Enrichment is performed via ultracentrifugation of gaseous compounds, electromagnetic mass separa- tion or selective laser dissociation or laser ionisation respectively. Most of these techniques are costly and complex, therefore the cost of highly enriched target material can contribute substantially to the over- all cost of the produced radioisotopes. The tables show the natural isotopic abundance of the target isotopes as an indication of the difculty of obtain- ing highly enriched material. Example of a double neutron capture reaction leading from stable 186W to the generator isotope 188W. However, all the mentioned enrichment techniques would be even more costly to implement if radioactive material has to be handled; the meth- ods take time (decay losses! However, in certain cases neutron capture does not produce the fnal radioisotope directly but 2. Tus the fnal radioisotope tron-rich isotopes with atomic masses ranging from difers chemically from the target and can therefore about 85 to 150. This indirect production capture of 235U is used, but fast neutron-induced usually leads to products in so-called non-carrier- fssion or photo-fssion of 238U are also being consid- added (n. The product elements difer chemically from carrier-free if no stable impurities of the product the actinide target and can be chemically separated isotope were present in the target material and other from all other products except other isotopes of chemicals used. Afer each Proton induced reactions such as (p,n) and (p,) separation new daughter activity will grow in and dominate for low proton energies (5 15 MeV) can be separated again. Also (p,2p) radioisotopes can only be reached from a stable reactions for the production of neutron-rich iso- target by two consecutive neutron captures. A par- topes such as 47Sc or 67Sc require protons of several ticularly high neutron fux is required to bypass tens of MeV. Finally with protons of 100 MeV or more, spallation becomes possible that allows the are deuterons and alpha particles. Triton and 3He population of isotopes further away from the tar- bombardment is considered too expensive or techni- get. Spallation with GeV protons produces a large cally challenging to warrant large scale use, while variety of products which gives the method more the heavy ion reactions (Li and heavier projectiles) universality but also makes the subsequent separa- populate many exit channels, thus reducing the tion steps more challenging. Chemical separation available yield in each channel and the resulting cannot remove radioisotopic impurities of the same radionuclidic impurity is impaired if no additional element, but sometimes a combination of chemi- measures are taken. When Physical mass separation in combination with traces of stable F2 are added to the gas target the chemical element separation is possible, e. However, it is chemical processes compared to the fuoride (F )- 113 of great interest for R&D applications to provide produced in water targets. Alpha-induced reactions provide access to prod- Most isotopes can be made by a number of ucts with two protons more than the target. When it comes to practical, economical high yield and high purity production the choice of projectile 2. At comparable production cross-sections but only in a few cases are these reactions regularly the highest production yields per beam current used for radioisotope production. The only important exception to this rule be used for the same purpose but they may lead to is 99mTc, that can be made efciently and pure by enhanced radiation doses to the patient if a fraction proton bombardment on 100Mo, but still is made of the radioisotope remains longer in the body (not far more economically and in a much more readily an issue for ventilation studies). Radioisotope generators are an elegant way out of the dilemma of contradicting half-life require- ments for use in patients and logistics. The mother isotope is loaded onto a generator and is usually chemi- cally bound to stay there quasi-infnitely. Afer each separation new daughter activity will grow separation of mother and daughter isotopes: liquid in and can be separated again. From the can be extracted again and again, even many half- user perspective it is more interesting to classify the lives afer the end of irradiation.

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