Review article

Technetium, the missing element Frederik A.A. de Jonge 1, Ernest K.J. Pauwels 2 1 Department of Nuclear Medicine, KCL Foundation, Leeuwarden, The Netherlands 2 Department of Diagnostic Radiology and Nuclear Medicine, Leiden University Hospital, Leiden, The Netherlands

Abstract. The history of the discovery of technetium is reviewed within the framework of the discovery and production of artificial radioactivity in the twentieth century. Important elements of this history are the accidental production of this element in a cyclotron in Berkeley, California, USA, a machine devised by Ernest Orlando Lawrence, and its subsequent discovery in 1937 by Carlo Perrier and Emilio Segrb in scrap metal parts sent by Lawrence to Palermo, Italy by mail. A detailed account is given of the steps taken; the history of the later discovery of the technetium-99m isotope in 1938 is likewise examined. Sources of natural and artificial technetium are briefly discussed. Key words: Technetium - Cyclotron - Artificial radioactivity

ments in the technical means of obtaining higher energies for particle bombardment, leading to the discovery of increasing numbers of isotopes and a number of new elements, particularly the transuranic series. Technetium, discovered in 1937 by Carlo Perrier and Emilio Segrb in scrap metal parts of a cyclotron, was the first element to have been produced by man before its actual discovery in nature. This article describes the history of the discovery of the element technetium as a contribution to the centennial celebration of the discovery of radioactivity. This history is of particular interest to our speciality of nuclear medicine as it is largely founded on the use of technetium. In this respect, a homage to all those involved in this exciting discovery seems eminently appropriate in 1996.

Eur J Nucl Med (1996) 23:336-344 Introduction

Prelude This year is the centennial of the discovery of radioactivity by Henri Becquerel, who noticed that naturally occurring uranium salts emit radiation capable of blackening a photographic plate [1]. This was soon followed by the discovery of two new radioactive elements, polonium [2] and radium [3] by Pierre and Marie Sklodowska Curie, who also introduced the term radioactivity. In the following years the nature of radioactivity was vigorously investigated, leading to better understanding of the natural occurring uranium decay series and the properties of c~-, ~- and 5'-rays. The tracer principle was born of the inability to separate a radioactive lead isotope from non-radioactive isotopes (Georg Charles De Hevesy [4]) and it did not take long before isotopes found their use in medical investigations. The discovery of artificial radioactivity in 1933 led to a wide search for radioisotopes and stimulated improveThis paper is dedicated to Carlo Perrier (1886-1948) and Emilio Segr6 (1905-1989) Correspondence to: EA.A. de Jonge, Department of Nuclear Medicine, KCL Foundation, RO. Box 850, NL-890I BR Leeuwarden, The Netherlands

When the first "periodic tables" were published (1869, D.I. Mendeleev, L. Mayer), only approximately 60 elements were known. The tables were constructed by listing the known elements by atomic mass and by noting that their chemical behaviour was similar after every eight elements (this being especially true for the elements with low mass). The table contained empty spaces and Mendeleev in 1871 accurately predicted the existence and several properties of at least three new elements: eka-aluminium, eka-boron and eka-silicium; eka meaning "first" in Sanskrit, thus indicating that the missing element would be the first chemically similar element in the periodic table. His predictions were soon confirmed by the discovery of, respectively, gallium in 1875, scandium in 1879 and germanium in 1886. He also speculated on the existence of eka-manganese and predicted an atomic weight of 100 but no other properties [5]. Looking at a modern periodic table it becomes clear that eka-manganese is technetium. This ekamanganese, however, was hard to find and its existence therefore unsure. Moreover, the discovery of isotopes (named as such by Soddy in 1913 [6]) cast doubts on the principle of ordering the elements by mass and thus on the very existence of the gap to be filled by eka-manganest.

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Element 43 found missing Great strides were being made in unraveling the secret of the atom. In 1897 J.J. Thomson discovered the electron, and a few years later measured its mass and charge. Ernest Rutherford in 1911 advanced the idea of an atom with a central nucleus where (most of) the mass was concentrated and which had a charge equal but of opposite sign to the (Z) electrons surrounding the nucleus. In this way, an integral number Z, the atomic number, could be associated with each element. Here was a new ordering principle for the elements which could replace atomic mass. This idea was put to good use by H.G.J. Moseley around 1913. He demonstrated experimentally that the frequency of characteristic (Kcz) X-rays emitted by an element is proportional to its atomic number Z. The element, mounted as the target anode, produced these Xrays under electron bombardment in an X-ray tube. In examining all the known elements from aluminium (Z = 13) up to gold (Z = 79), gaps appeared in the measured X-ray frequencies between certain elements, leading to the conclusion that elements with Z = 43, 61, 72 and 75 were missing [7]. Moseley's work was confirmed by the discovery of hafnium (Z = 72) in 1923 and rhenium (Z = 75) in 1925; promethium (Z = 61) remained missing until 1945, when it was discovered as a fission product. Moseley's work clearly supported the idea of an element eka-manganese as predicted earlier by Mendeleev, but the question was still where to look for it.

Early claims to the discovery of element 43 Various workers claimed to have discovered an element with Z = 43 in naturally occurring ores and proposed such names as polinium (1828), ilmenium (1846), davyum (1877), lucium (1896) and nipponium (1908) [8]. These claims, however, could not be confirmed by others and often were caused by mistaking an already known element for the missing element. There was even an appeal to the scientific community in 1925 to name element 43, if it were discovered, "moseleyum" in honour of Moseley and his work [9]. In June 1925, Noddack, Tacke (later Tacke-Noddack) and Berg announced their discovery of one of the missing elements (Z = 75), and provided proof in the form of the X-ray spectrum; they decided to name the element rhenium in honour of the river Rhine. In a short time this discovery was confirmed by others and 120 kg per year was being produced in Germany by 1930. At the same time they claimed discovery of element Z = 43, again on the basis of X-ray spectrum analysis, and this element they named masurium for Masurenland in East Prussia. The extent to which this claim was taken seriously can be judged from the fact that as late as 1941 the Gmelin Handbook of Inorganic Chemistry published a volume entitled Masurium [10], noting, however, that X-ray spectrographic proof of the existence of masurium in

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naturally occurring minerals had not been found by others. Segrb relates how in 1937 he visited the Noddacks to discuss with them the properties of element Z = 43 and left with the impression that "it was unlikely that they had clear-cut results" as they were unable to show him the X-ray plates with their spectrographic evidence. The Noddacks claimed that the plates had been accidentally broken and failed to give a good reason for not making new plates [ 11 ].

Nuclear physics and machines In 1932 three great discoveries were made: the neutron was discovered by James Chadwick on the basis of work done by Frdddric Joliot and Irbne Curie, the positron was discovered in cosmic rays by Carl D. Anderson and Harold Urey discovered deuterium, the hydrogen isotope with a nucleus consisting of a proton plus a neutron. Now it was clear that the nucleus is composed of Z protons and N neutrons with Z electrons surrounding it. The positron proved to be the first of many nuclear particles and played a role in the discovery of artificial radioactivity. Deuterium would play an important role in accelerators as a bombarding particle in nuclear reactions. Further investigation in the nucleus would largely depend on high-energy bombardments in different types of machines. In 1919 Rutherford published a paper describing the first observation of a nuclear disintegration. Under o~-particle bombardment nitrogen gas is seen to release protons according to the 14N(o~,p)170 reaction. The a-particles had relatively low energies. Rutherford realized that "if.. particles., of still greater energy were available, we might expect to breakdown the nucleus..." [12]. In 1932 his dream came true: in the Cavendish Laboratory in Cambridge, headed by Rutherford, John D. Cockroft and Ernest T.S. Walton designed a voltage multiplier circuit to obtain the necessary high accelerating voltages. In 1932 they achieved the first nuclear disintegration by artificially accelerated particles (protons of 770 keV) by bombarding lithium (Z = 3) atoms which resulted in an unstable beryllium nucleus immediately decomposing into two (x-particles, according to the reaction 7Li(p,cz)cz. This result was reproduced - with some difficulty [13] - by Ernest Orlando Lawrence in Berkeley, California, using his newly developed magnetic resonance accelerator, later dubbed (1935) the cyclotron.

Cyclotrons Lawrence gained the inspiration for the cyclotron by an article by Rolf Wider6e in 1928 in which he described the first two-stage linear accelerator [13]; in this machine a relatively low voltage was used to accelerate particles in successive stages, thus circumventing the need to apply direct high voltages. Lawrence realized that he could do even better: by applying a magnetic field per-

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Fig. 1. M.S. Livingston(l@) and E.O. Lawrence(right) in front of the 27-inch cyclotronin the Radiation Laboratoryat the University of California,Berkeley, 1934. This was the cyclotronfrom which the molybdenumstrip came in which technetiumwas discovered in 1937. Reproducedby permission of the LawrenceBerkeley Laboratory,courtesyof the American Institute Physics,Emilio Segr8 Visual Archives)

pendicular to the plane in which the particles were moving they would be forced to move in a circular path. By applying a voltage difference the particles would accelerate across the gap between the two circular halves (the "dees" or "D's" on account of their shape) of the machine, and by switching the direction of the voltage by the time the particles reached the gap again they could be accelerated again.., and again and again. As the particles picked up speed they would tend to spiral outwards, increasing the length of the spiral path in the "dee" each turn by just so much that the time spent in the "dee" would remain (almost) constant. Choosing the correct frequency of voltage switching one would obtain repeated acceleration (hence the term "resonance") at each crossing of the gap. The principle was first published by Lawrence and Edlefsen in 1930 and in that year they built a first model; by the end of 1930 M. Stanley Livingston and Lawrence had a working 4-inch cyclotron which by 2 January 1931 produced 80-keV hydrogen ions using only a voltage of around 1000 volts. By 9 January 1932, they had an l 1-inch model producing 1220 keV protons with a 4000-V difference acros the "dees" (thus these protons had been accelerated across the gap approximately 300 times); later, in 1932, they were able to obtain nuclear disintegrations with this ll-inch model, confirming the results of Cockroft and Walton. By this time Lawrence was already constructing a larger 27inch cyclotron at the Radiation Laboratory (Fig. 1) and

in April 1933 he started accelerating the newly discovered deuterons (deuterium ions) in it, reaching 3-MeV deuterons in 1934 and 6.2-MeV deuterons in 1936 {13].

Artificial radioactivity Joliot and Curie had the disappointment of having missed discovering the neutron in January 1932 and of having missed discovering the positron later in 1932, both times in fact noticing the indicated particle but interpreting it wrongly. However, 1933 was their "lucky" year. In July 1933 they discovered that certain substances emitted positrons with a continuous energy spectrum (much like the continuous [3-ray spectra). Their further investigations resulted in a one-page paper, published on 10 February 1934 [14], detailing their striking find: aluminium, boron and magnesium bombarded with c~-particles from a polonium source became radioactive. They demonstrated that the resulting radioactive species were chemically different from the parent compounds thus effectively having transmutated one element into another, e.g. stable aluminium turned into radioactive phosphorus which decayed by positron emission to stable silicium. Artificial radioactivity was born.

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More artificial radioactivity Lawrence, on hearing this exciting news, immediately bombarded carbon with deuterons in the 27-inch cyclotron and observed induced radioactivity. He, too, had missed an important discovery simply because he did not notice it, not being prepared to look for radiation after switching off the cyclotron beam. Enrico Fermi, in Rome, argued that neutrons would be more efficient than c~-particles in transmutation as they would not be electrically repulsed from the nucleus as or-particles would be. He started systematic neutron bombardment of all the elements with a radon-beryllium source (the radon being obtained from a so-called radon generator containing a radium source). At first there was no success with H, Li, Be, B, C, N or O but then with F he was successful. He and his team consisting of Franco Rasetti, Edoardo Amaldi, Oscar D'Agostino, Emilio Segr~ (and later Bruno Pontecorvo) went on bombarding elements and in 3 years made almost 40 new radioactive species and discovered that neutrons slowed down in paraffin were even more effective than fast neutrons in inducing radioactivity [12]. This principle of neutron moderation would be a key element in the later development of the nuclear reactor. In an amusing story Segrb relates that in 1934 he was sent out, being the son of a businessman, to buy samples of all the known elements. In the chemical shop run by Signor Tricolli, who took pride in having an ample stock of all the elements as well as in his knowledge of Latin, Segr~ asked for a sample of masurium; the answer was "Nunquam vidi" (I have never seen it) [11]; only a few years later did Segrb realize that masurium as such did not exist. Following Fermi's lead, Lawrence realized that the cyclotron could be used as a neutron source, too: by bombarding beryllium with a deuteron beam a secondary beam of neutrons is formed; in this way his cyclotron could confirm Fermi's results and acquired a new role as a neutron source.

Bigger cyclotrons and medicine Bigger cyclotrons meant higher energies and stronger beams of charged particles, stronger secondary beams of neutrons and easier production of radioisotopes in larger amounts. At the time it was thought that cheap artificially produced isotopes could perhaps replace expensive radium. The 27-inch cyclotron was partially dismantled to allow insertion of larger pole pieces to enlarge the area of the magnetic field and a bigger vacuum chamber to obtain a bigger radius and thus higher energies. Thus by mid 1937 the enlarged version - the 37-inch model was operational. In 1935 biological experiments, in collaboration with John Lawrence, Ernest Lawrence's brother, had been

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commenced to look into the radiobiological effects of neutron radiation. Further medical work was done with 32R 24Na and 59Fe, isotopes produced by the cyclotron. Later the 60-inch cyclotron was built specifically for medical purposes: to produce more of these isotopes and to make possible medical experiments with neutron irradiation of cancer, in the hope that this would be more efficacious than X-ray therapy. The cyclotron as an invention seemed to have unlimited possibilities and was to win Lawrence the Nobel prize in 1939. Segr~ had already been much impressed by its possibilities for producing large amounts of radioactivity; in 1935 Lawrence sent 1 mCi of 24Na by letter to Fermi (then in the United States) in response to Fermi's suggestion that Lawrence had perhaps made a mistake in offering him 1 mCi and had meant 1 gCi [11]! It is not surprising that Segrb, by now experienced in radiochemistry due to his work with Fermi in Rome, wanted to meet this New World wonder.

The stage is set: Segr~ meets Lawrence Segr~ accompanied Fermi in 1933 and 1935 on visits to the United States to attend the famous summer school on theoretical physics at the University of Michigan at Ann Arbor. Both men also developed close contacts with physicists in the United States. In 1935 Segr~ spent some time working in Columbia University (New York) on neutron absorption whilst awaiting the outcome of his application for the chair of physics at the University of Palermo, Sicily. Because of the deteriorating political situation in Italy related to the rise of fascism, Segr~ was already considering staying in the United States if his appointment were not to come through. At the end of October 1935 word of his appointment finally came and Segr~ returned to Italy. Arriving in Palermo, Segr~ started to (re)organise the institute and found time to build some instruments for radiation detection with which he hoped to do research, although he was lacking radioactive sources. In the summer of 1936 Segr6 and his wife visited the United States. Again, politically motivated worries and professional interests were the driving force. Segrb wanted to visit Columbia University; his wife, who was pregnant, did not tolerate the humid weather in New York. They decided to leave for a better climate, moving on to Berkeley, California, giving Segrb the chance to visit the Radiation Laboratory, see the cyclotron and meet Lawrence. During his short stay there Segr~ noticed "that there was a lot of radioactive metal scrap lying around" [11]. He had found his radioactive sources to do research in Palermo; the first metal scrap parts arrived in Palermo in Segr6's suitcase!

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Element 43 discovered In this first "shipment" of radioactive metal scrap, Segrb found a large contamination of 32p and radioactive species of cobalt, zinc and possibly silver. The 32p was there presumably as a result of its production for medical purposes, as noted above. Segra, recognizing its potential as a biological tracer, managed to interest a professor of physiology, Camillo Artom, in its application; together they studied phospholipid metabolism with 32p as a tracer [11], following in the footsteps of Hevesy, who was the first to use 32p as a tracer [4]. Segrb wrote to Lawrence saying "We would like very much to have more copper" and "I think you can send any substance in a letter" [13]. And this is what Lawrence did: "He salvaged more copper and the molybdenum strip that protected the dee edge at the (beam) exit slot. He had it all cut up and sent in several letters" [13]. The metal parts were derived from the 27-inch cyclotron which around this time had been opened for repairs and/or enlargement (see above). Molybdenum was used in this particular place in the cyclotron because of its high melting point, which rendered it refractory to the heating effect of bombardment. Segrb writes in his biography that when he received the molybdenum strip he immediately realized "that it might contain element 43" and that he made a note to that effect in his laboratory notebooks for 1937 [11]. He decided to investigate this possibility by showing that the radioactivity present could not be ascribed to radioisotopes of other known elements by separating it from these elements according to well-established chemical means and by investigating the chemical properties of the new element. He asked Professor Carlo Perrier from the mineralogy department to help with the chemical investigations. By June 1937 they had reached their goal: element 43 had finally been found and, to add to their success, not in nature but as the first man-made element. In the meeting of the R. Accademia Nazionale dei Lincei on 4 June 1937, in Rome, a communication from Carlo Perrier and Emilio Segr6 was read by Nicola Parravano under the title "Alcune proprietd chimiche dell'elemento 43" and subsequently published [15] (title page reproduced in [16]). A first international announcement of their discovery appeared in Nature on 31 July 1937 [17]. On every occasion, Lawrence's help was generously acknowledged and the remarkable capabilities of the cyclotron were emphasized; in a letter to Lawrence, Segr~ even referred to the cyclotron as "a sort of hen laying golden eggs" [13]. The above account of how the molybdenum strip reached Segra in Palermo seems the most correct version as it is documented by letters between Lawrence and Segrb cited in Heilbron and Seidel and confirmed by Segra in his biography; it differs from the history as written by Segre in his review of the discovery of element 43 [16] as he states there that he took it with him in his suitcase to Palermo. It is definitely more correct than

the version given by Brucer [18] in his A chronology of nuclear medicine, according to which Perrier and Segr6 in Rome received a small package by mail, sent to Fermi in Rome by Lawrence, containing a molybdenum target in which they then discovered technetium-99m. It will be clear from the above that it was not a consciously placed molybdenum target and that Perrier and Segra were not in Rome but that it was mailed to Segre in Palermo. Moreover, any short-lived activity (technetium99m or its parent molybdenum-99) would have decayed in view of the considerable interval (approximately 6 weeks) between the end of irradiation in the cyclotron and the beginning of their investigations [19]; the mailing time of several weeks by boat is included in this interval. They did not name the element yet, largely in view of the older claims of the Noddacks and also because unwelcome suggestions were made for names celebrating fascism or Sicily, such as Trinacrium (from Trinacria, an ancient Greek name for Sicily) [11]. Segre writes that he regrets having asked Parravano to read their communication as he experienced "manifest signs of anti-semitism" on this occasion [11]. Clearly, the political situation was worsening and once again the United States beckoned.

Actual steps taken in the discovery [19] The molybdenum strip had been in the cyclotron for a considerable time ("bombarded by a strong deuteron beam for some months"). Given that in the molybdenum strip one would expect reactions due to deuteron bombardment and/or the secondary neutrons always generated in the cyclotron, the activity might have been due to isotopes of (a) molybdenum and columbium (now known as niobium) from deuteron or neutron reactions or of (b) zirconium only from fast neutron reactions and of (c) element 43, due to deuteron (d,n)-type reactions. The face o f the molybdenum strip struck by the cyclotron beam showed much higher radioactivity than the other side, suggesting that the induced radioactivity was due to a charged particle reaction and not to neutrons, which would have induced radioactivity in the whole strip. After the molybdenum strip had been dissolved in aqua regia (HNO 3 + HC1), careful chemical analysis showed that the induced activity was separable from zirconium, columbium and molybdenum, thus forming a negative argument for the presence of an isotope of element 43. As a (stable) isotope of element 43 was not available in weighable amounts, no direct confirmation by way of a carrier experiment leading to precipitation of the induced activity could be performed; positive confirmation, however, would come some time later. Chemically the radioactivity was easily separable from manganese and behaved more like rhenium, a result which was expected for element 43; a notable differ-

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341 ence was the lack of volatilization of the element 43 activity in a hydrochloric acid current (a method used to separate molybdenum from rhenium), thus achieving a separation from rhenium. Further studies showed half-lives of 90, 80 and 50 days, suggesting that possibly more than one isotope was present [20], although the authors did not have great confidence in the latter two half-life measurements; in new experiments in 1938 with a new molybdenum target bombarded in the cyclotron, Cacciapuoti found halflives of 90 and 62 days [21]; retrospectively Segr~ thinks that in the original sample they studied, only two isotopes were present: one with mass number 97 and a 90day half-life, the second with mass number 95 and a 61day half-life [l 1]. In modern notation, element 43 was thus discovered as 97mTc (half-life 90 days), formed as a 96Mo (d,n) reaction product, and the original molybdenum strip might also have contained 95mTc (half-life 60 days, current estimate), formed as a 94Mo (d,n) reaction product; in both cases the metastable condition of the isotope was not recognized.

Segr~ becomes a "refugee at Berkeley" [11] and discovers isomerism in element 43 In Palermo, Segra planned to search for short-lived isotopes of element 43. For that, however, he would have to go to their source, Berkeley, as letters coming by boat were too slow to carry such activities. He decided to spend the summer in Berkeley and arrived in New York on 13 July 1938. A few days later he knew he would not return to Italy: a new charter of antisemitism had been published and legal measures - including Segre's probable discharge as a professor or worse - were likely to follow. Like so many others in this period he had become a refugee but he had the good fortune that by October 1938 his wife and son were able to join him in Berkeley. Soon after arrival in Berkeley he made contact with Glenn T. Seaborg and they started working together on the experiments already planned. By bombarding a molybdenum strip with 8-MeV deuterons in the 37-inch cyclotron [22] they obtained a radioactive molybdenum species (half-life 65 h) which decayed by [3-emission to a short-lived isotope (half-life 6 h) with novel properties: it emitted a line spectrum of electrons (as opposed to a broad band spectrum as in [3-decay) with an energy of approximately 110 keV, due to "conversion electrons of a T ray of about 130 keV" [23]. They quickly confirmed chemically that this was indeed an isotope of element 43, adding more proof by showing that the characteristic Kc~ X-ray following the ejection of the conversion electron had the energy expected of an isotope of element 43 (by absorption studies in molybdenum Z = 42, columbium Z = 41 and zirconium Z = 40 which showed greatly increased absorption in zirconium due to the K edge absorption discontinuity).

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They proposed that the "simplest and most reasonable explanation for these facts is the existence of an excited state in this isotope of element 43 which reverts to the ground state.., with a half-life of 6 h" [23]. Their discovery was an early example of nuclear isomerism with the interesting feature of a high rate of internal conversion of the T-ray. On the advice of Robert Oppenheimer, then professor of theoretical physics at Berkeley, who considered the high degree of internal conversion of the T-ray "impossible", Lawrence asked them to delay publication, thereby giving Pontecorvo the chance to be the first to publish a similar case of nuclear isomerism in rhodium [13]. Seaborg and Segr~ later resubmitted their letter and it was finally published in the Physical Review on 14 October 1938 [23]. In a further publication in 1939 the experiments and their results leading to the discovery of the isomeric transition were given in more detail [24], and this article has a photograph of the electron line spectrum. The estimates of electron energies are refined (K and L conversion electrons of respectively 116 and 133 keV, from a 7ray of 136 keV). Details of the absorption studies mentioned above are given and a direct photograph of the (naturally emitted) Kc~ X-ray line was obtained with a bent crystal spectrograph. Thus nature had provided a way of observing directly the Kc~ X-ray line which had been found missing in Moseley's original X-ray work! The parent molybdenum was considered to be either 99Mo or 1°1Mo. It was only later demonstrated that the isomeric technetium isotope had 99Mo as its parent. Thus, adding the "m" for metastable, the later chosen convention to denote a (relatively long-lived) excited state, we can recognize 99mTc as being the isotope made in Lawrence's cyclotron by Segr~ and Seaborg in 1938. All radioactivity measurements performed in these investigations of element 43 were done with an ionization chamber of a type Segr~ had been accustomed to working with in Rome and Palermo and which he considered superior to the radiation detection instruments then in use in the Radiation Laboratory. Segr~ built it from parts left in Berkeley by his old friend Franco Rasetti in 1935 and it was connected to a DC amplifier made by Lee DuBridge [11]. Segr~'s electrometer was subsequently used in many more investigations in the Radiation Laboratory and served in the detection of 3H, 14C and plutonium; it is now a museum piece on display at the Smithsonian Institution in Washington D.C. (a photograph can be found in Lawrence and his Laboratory [13]).

Naming element 43: technetium is born Perrier and Segr~ decided not to name the element they had discovered in view of earlier claims and other unwelcome naming suggestions as related above. After the Second World War, in a lecture entitled "The making of the missing chemical elements" given in Leeds, UK, for the Royal Institute of Chemistry on 29 October 1946

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Fig. 2. Emilio Segr6 in the spring of 1952. The equations on the board indicate the reactions that produced elements or isotopes discovered by Segr6: technetium, astatine and plutonium-239. (Reproduced by permission of Mrs. Rosa M. Segr6)

[25] and published in the 4 January 1947 issue of Nature, Paneth suggested that the time had come to give the artificially made elements with Z = 43, 61, 85 and 87 and the transuranics their proper place in the periodic system. He proposed to honour the claim of Segr6 and Perrier as having discovered element 43, arguing that their discovery of the element as an artificially produced isotope was no different than the discovery of a new element in nature. On his suggestion, Perrier and Segr6 published a letter in the same issue of Nature, proposing the name "technetium" with the symbol "Tc", from the Greek '"c~)~vq'cdg", artificial, in recognition of the fact that it was the first element to be discovered by producing it artificially as opposed to discovery in nature [26]. The International Union of Chemistry officially accepted the proposal in September of 1949 and the element is now universally known by this name.

Technetium in nature For many years it was thought that technetium did not occur in nature as extensive searches especially in molybdenum- or rhenium-containing ores were unsuccessful. From a theoretical point of view isotopes of technetium were all expected to be unstable, and later studies showed that technetium isotopes are all relatively shortlived in comparison to the age of the earth's crust. Thus, any technetium produced in primordial times when the earth's crust was formed would have effectively decayed without a trace, explaining these negative searches [27].

The first evidence for the natural occurrence of technetium was found in the discovery of technetium X-ray spectra in certain stars in 1952 [28], leading to the hypothesis of stars as continuous "chemical factories" synthesizing elements in the "s process" (slow-time-scale neutron capture); this probably also explains why technetium lines are missing from the spectrum of the sun as this star is not in the "s process" phase of its existence

{27]. On earth, spontaneous fission of 238U proved a source of ongoing formation of technetium isotopes. In 1961 Kenna and Kuroda reported the first isolation of natural 99Tc [29]; approximately 1 ng 99Tc was isolated from several kilograms of Belgian Congo pitchblende, the amount of technetium found being in accordance with calculations assuming its origin from spontaneous fission of 238U. Later studies also suggested that (naturally occurring) neutron-induced fission of 235U can significantly contribute to the 99Tc content [27]. So, technetium is not a completely artificial element.

Sources of artificial technetium The importance of technetium for nuclear medicine does not need further explanation here; industrially 99Tc has found some applications as a chemical process catalyst, an alloying agent, a corrosion inhibitor and a reactor burn-up indicator [30]. However, not enough technetium is present on our earth to sustain the needs of medical or industrial users. Artificial production in cyclotrons or

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343 nuclear reactors is therefore essential for its continued use. Soon after the discovery of spontaneous fission of uranium in 1938, Wu and Segr~ demonstrated the occurrence of 99mTc in fission products of uranium bombarded with neutrons from the Berkeley cyclotron [31]. The world's first nuclear reactor went critical on 2 December 1942 under the guidance of Enrico Fermi. During and after the Second World War many more were built and in September 1946 the first weighable amounts of technetium as 99Tc were produced by neutron irradiation of molybdenum in a nuclear reactor in Oak Ridge, Tennessee [9]. 99Tc can now be obtained in large quantities as a fission product from nuclear reactors. The nuclear reactor is currently the major source of 99mTc in the form of its parent 99Mo. The 99Mo is obtained either as a direct fission product or from neutron activation of natural molybdenum or 98Mo-enriched targets according to a (n,T) reaction. The latter suffers from the disadvantage of low specific activity and it is the fission-produced 99Mo which is most widely used. Cyclotron-produced 99Mo/99mTc has the disadvantage of a high content of radionuclidic impurities requiring substantial purification efforts [32].

The discoverers honoured Emilio Segrb (1905-1989, Fig. 2) participated in several other radioisotope discoveries, notably astatine (Z = 85, the heaviest halogen) and plutonium-239 (Z = 94, used in the second atom bomb) and was considered one of the ten best radiochemists in a survey held in the United States in 1947 [11]. Contrary to his own hopes, he would not get the Nobel prize for his radiochemistry work, the 1951 Chemistry Nobel Prize going to McMillan and Seaborg for their discoveries in the chemistry of transuranium elements. He received the Nobel prize in 1959 together with Owen Chamberlain for their discovery of the antiproton, made in the bevatron, a further development of the cyclotron capable of accelerating protons to 6 GeV. Carlo Perrier (1886-1948) was not honoured in this direct way. Indirectly, however, Segrb has honoured him by mentioning "his superior chemical ability" [16] and gave him similar praise on other occasions [11, 33], making it clear that Perrier's contribution was essential. A photograph of Professor Carlo Perrier, dating from 1947, can be found in Segr~'s review of the discovery of technetium [ 16].

Conclusion Carlo Perrier and Emilio Segr~ discovered technetium, the missing element, in 1937 in molybdenum scrap metal generously given to them by Ernest Orlando Lawrence. Due to Lawrence's cyclotron, it was the first element produced artificially before its discovery in nature.

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Later, in 1938, Glenn T. Seaborg and Emilio Segrb discovered 99mTc, again a cyclotron product. In nature, one can only find minute amounts of techetium. We - mankind - have made it available for our own use, although production facilities for 99Mo/99myc for medical purposes are still limited [34]. Nuclear medicine is currently the most immediate benefit to mankind of the discovery of technetium, as Segrb and Seaborg themselves were rightly proud to point out [16, 22]. Our duty as members of the nuclear medicine community is to ensure that their discoveries will continue to benefit mankind.

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