Charles Pecher (26 November 1913 – 28 August 1941) was a Belgian pioneer in nuclear medicine. He discovered and introduced

strontium-89 Strontium-89 () is a radioactive isotope of strontium produced by nuclear fission, with a half-life of 50.57 days. It undergoes beta decay, β− decay into yttrium-89. Strontium-89 has an application in medicine. History Strontium-89 was firs ...

in medical therapeutic procedures in 1939. He was the first to report a possible therapeutic role for the beta emitting radionuclide strontium-89 in the palliation of bone pain associated with metastatic bone disease. His

autoradiograph An autoradiograph is an image on an X-ray film or nuclear emulsion produced by the pattern of decay emissions (e.g., beta particles or gamma rays) from a distribution of a radioactive substance. Alternatively, the autoradiograph is also availab ...

ies of animals or organs after administration of strontium-89 or phosphorus-32 started the development of bone

scintigraphy Scintigraphy (from Latin ''scintilla'', "spark"), also known as a gamma scan, is a diagnostic test in nuclear medicine, where radioisotopes attached to drugs that travel to a specific organ or tissue (radiopharmaceuticals) are taken internally a ...

. The groundbreaking work of Pecher was forgotten for decades due to the classification of information linked to the

Manhattan project The Manhattan Project was a research and development program undertaken during World War II to produce the first nuclear weapons. It was led by the United States in collaboration with the United Kingdom and Canada. From 1942 to 1946, the ...

. The therapeutic use of ⁸⁹Sr was only approved in 1993 for the palliative treatment of breast and prostate cancers metastatic to the bones for use in the US and became the first bone-seeking radiopharmaceutical that came into widespread use.

Biography

Born in Antwerp on 26 November 1913, Pecher was the son of the liberal politician Édouard Pecher and Emilie Speth. After secondary studies at the Koninklijk Atheneum Antwerpen (1932), he continued with a university education in both physics and medicine. He became assistant of professor Pierre Rylant at the

Université libre de Bruxelles The (French language, French, ; lit. Free University of Brussels; abbreviated ULB) is a French-speaking research university in Brussels, Belgium. It has three campuses: the ''Solbosch'' campus (in the City of Brussels and Ixelles), the ''Plain ...

, where he specialized in biophysics. Pecher pioneered in fundamental

neurophysiology Neurophysiology is a branch of physiology and neuroscience concerned with the functions of the nervous system and their mechanisms. The term ''neurophysiology'' originates from the Greek word ''νεῦρον'' ("nerve") and ''physiology'' (whic ...

through his evidence of random processes in the nervous system. He received his doctor's degree in 1939. His medical studies were awarded the Armand Kleefeld Prize and earned him a scholarship from the

Belgian American Educational Foundation The Belgian American Educational Foundation (BAEF) is an educational charity. It supports the exchange of university students, scientists and scholars between the United States and Belgium. The foundation fosters the higher education of deserving ...

to continue his research in the United States. On 1 August 1939, Pecher married fellow researcher Jacqueline Van Halteren (31 May 1915 – 16 September 2013) and the couple traveled to the US the following month. Pecher first worked at Harvard University with

Edwin Cohn Edwin Joseph Cohn (December 17, 1892 – October 1, 1953) was a protein scientist. A graduate of Phillips Academy, Andover 911 and the University of Chicago 914, PhD 1917 he made important advances in the physical chemistry of proteins, and was r ...

and

George Kistiakowsky George Bogdanovich Kistiakowsky (, ; – December 7, 1982) was a Ukrainian-American physical chemistry professor at Harvard who participated in the Manhattan Project and later served as President Dwight D. Eisenhower's Science Advisor. B ...

. In 1940, he was appointed Research Fellow in the Radiation Laboratory at the

University of California, Berkeley The University of California, Berkeley (UC Berkeley, Berkeley, Cal, or California), is a Public university, public Land-grant university, land-grant research university in Berkeley, California, United States. Founded in 1868 and named after t ...

. After two intense years, Pecher became entangled in the Second World War. In 1940 the

Belgian Government in exile The Belgian Government in London (; ), also known as the Pierlot IV Government, was the government in exile of Belgium between October 1940 and September 1944 during World War II. The government was wikt:tripartite, tripartite, involving minis ...

decided to raise a military unit from pre-war Belgian émigrés and soldiers rescued from

Dunkirk Dunkirk ( ; ; ; Picard language, Picard: ''Dunkèke''; ; or ) is a major port city in the Departments of France, department of Nord (French department), Nord in northern France. It lies from the Belgium, Belgian border. It has the third-larg ...

and called up all Belgian nationals worldwide to join the

Free Belgian Forces The Free Belgian forces (, ) were soldiers from Belgium and its colonies who fought as part of the Allied armies during World War II, after the official Belgian surrender to Nazi Germany. It is distinct from the Belgian Resistance which exist ...

. A battalion was formed in Canada from Belgian émigrés in the Americas. Pecher saw himself faced with a choice between his patriotic duty and his scientific calling, with the complicating factor of American pressure to remain in work in a domain whose military relevance was fully recognized, with all the secrecy that this entails. In the end, Pecher responded to his convocation for the Belgian army in the United Kingdom. In

Joliette Joliette () is a city in southwest Quebec, Canada. It is approximately northeast of Montreal, on the L'Assomption River and is the seat of the Regional County Municipality of Joliette. It is considered to be a part of the North Shore of G ...

, where he was supposed to board for Europe, he died on 28 August 1941. A verdict of suicide was derived from the high dose of barbiturates in his body. His daughter Evelyne was born two months later.

Work

Between 1938 and 1940,

Ernest O. Lawrence Ernest Orlando Lawrence (August 8, 1901 – August 27, 1958) was an American accelerator physicist who received the Nobel Prize in Physics in 1939 for his invention of the cyclotron. He is known for his work on uranium-isotope separation for ...

and William M. Brobeck developed and built a 60-Inch cyclotron, which accelerated deuterons to 19 MeV, the first cyclotron capable of producing medically useful radioisotopes. It was housed in the Crocker Laboratory. In 1940, Pecher was appointed Research Fellow in the Radiation Laboratory of

at the

, where he produced radioisotopes in the cyclotron under the supervision of John H. Lawrence and used them as radioactive tracers. The bones are largely composed of calcium and phosphorus in the form of

tricalcium phosphate Tricalcium phosphate (sometimes abbreviated TCP), more commonly known as Calcium phosphate, is a calcium salt of phosphoric acid with the chemical formula Ca3(PO4)2. It is also known as tribasic calcium phosphate and bone phosphate of lime (BPL). ...

. W. Wesley Campbell and David M. Greenberg and later Pecher demonstrated using radioactive tracers that calcium is almost entirely stored in the bones with small traces being distributed in the

soft tissue Soft tissue connective tissue, connects and surrounds or supports internal organs and bones, and includes muscle, tendons, ligaments, Adipose tissue, fat, fibrous tissue, Lymphatic vessel, lymph and blood vessels, fasciae, and synovial membranes.� ...

s. For this reason, the metabolism of calcium attracted very early the interest of physicians looking for applying radioisotopes of calcium for therapeutic purposes. Pecher predicted and then demonstrated that strontium, which belongs to the same

group A group is a number of persons or things that are located, gathered, or classed together. Groups of people * Cultural group, a group whose members share the same cultural identity * Ethnic group, a group whose members share the same ethnic iden ...

in the

periodic table The periodic table, also known as the periodic table of the elements, is an ordered arrangement of the chemical elements into rows (" periods") and columns (" groups"). It is an icon of chemistry and is widely used in physics and other s ...

, was absorbed by the human body in a manner similar to calcium. His work with strontium-89, a calcium analogue, eventually led to its administration to a terminal patient with

osteoblastic Osteoblasts (from the Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts function ...

metastases Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

from a metastatic

carcinoma Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesoder ...

of the prostate. A posthumously published

y of an amputated leg with strontium-89 is the first human bone

. It was the third medical radioisotope, after

phosphorus-32 Phosphorus-32 (32P) is a radioactive isotope of phosphorus. The nucleus of phosphorus-32 contains 15 protons and 17 neutrons, one more neutron than the most common isotope of phosphorus, phosphorus-31. Phosphorus-32 only exists in small quantiti ...

and

iodine-131 Iodine-131 (131I, I-131) is an important radioisotope of iodine discovered by Glenn Seaborg and John Livingood in 1938 at the University of California, Berkeley. It has a radioactive decay half-life of about eight days. It is associated with nu ...

introduced respectively by

John H. Lawrence John Hundale Lawrence (January 7, 1904 – September 7, 1991) was an American physicist and physician best known for pioneering the field of nuclear medicine. Background John Hundale Lawrence was born in Canton, South Dakota. His parents, Carl Gu ...

and

Joseph G. Hamilton Joseph Gilbert Hamilton (November 11, 1907 – February 18, 1957) was an American professor of Medical Physics, Experimental Medicine, General Medicine, and Experimental Radiology as well as director (1948–1957) of the Crocker Laboratory, ...

. Pecher demonstrated using two cows the Sr-89 transfer to milk. Pecher filed a patent in May 1941 for the synthesis of strontium-89 and

yttrium-86 Natural yttrium (39Y) is composed of a single isotope, yttrium-89. The most stable radioisotopes are 88Y, which has a half-life of 106.6 days, and 91Y, with a half-life of 58.51 days. All the other isotopes have half-lives of less than a day, exce ...

using cyclotrons and described the use of strontium for therapeutic uses. The groundbreaking work of Pecher was forgotten for decades due to the classification of information linked to the

and the American nuclear weapons program. While ⁸⁹Sr with a half-life of 50.6 days is used to treat

bone cancer A bone tumor is an neoplastic, abnormal growth of tissue in bone, traditionally classified as benign, noncancerous (benign) or malignant, cancerous (malignant). Cancerous bone tumors usually originate from a cancer in another part of the body su ...

, ⁹⁰Sr is an isotope of concern, with a half-life of 28.90 years, following a

fallout Nuclear fallout is residual radioactive material that is created by the reactions producing a nuclear explosion. It is initially present in the radioactive cloud created by the explosion, and "falls out" of the cloud as it is moved by the ...

from

nuclear weapons A nuclear weapon is an explosive device that derives its destructive force from nuclear reactions, either nuclear fission, fission (fission or atomic bomb) or a combination of fission and nuclear fusion, fusion reactions (thermonuclear weap ...

and

nuclear accidents A nuclear and radiation accident is defined by the International Atomic Energy Agency (IAEA) as "an event that has led to significant consequences to people, the environment or the facility." Examples include lethal effects to individuals, la ...

as it's a common

fission product Nuclear fission products are the atomic fragments left after a large atomic nucleus undergoes nuclear fission. Typically, a large nucleus like that of uranium fissions by splitting into two smaller nuclei, along with a few neutrons, the releas ...

. Its presence in bones can cause bone cancer, cancer of nearby tissues, and

leukemia Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...

United States Atomic Energy Commission The United States Atomic Energy Commission (AEC) was an agency of the United States government established after World War II by the U.S. Congress to foster and control the peacetime development of atomic science and technology. President Harry ...

commissioned in 1949 an investigation, codenamed

Project GABRIEL Project GABRIEL was an investigation to gauge the impact of nuclear fallout resulting from nuclear warfare. The United States Atomic Energy Commission surmised that the radioactive isotope strontium-90 (Sr-90) presented the greatest hazard to life ...

, to gauge the impact of radioactive fallout resulting from

nuclear warfare Nuclear warfare, also known as atomic warfare, is a War, military conflict or prepared Policy, political strategy that deploys nuclear weaponry. Nuclear weapons are Weapon of mass destruction, weapons of mass destruction; in contrast to conven ...

. It surmised that the radioactive isotope

strontium-90 Strontium-90 () is a radioactive isotope of strontium produced by nuclear fission, with a half-life of 28.79 years. It undergoes β− decay into yttrium-90, with a decay energy of 0.546 MeV. Strontium-90 has applications in medicine a ...

(Sr-90) represented the most serious threat to human health from nuclear fallout. This resulted in the commissioning of Project SUNSHINE, which sought to examine the long-term effects of nuclear radiation on the

biosphere The biosphere (), also called the ecosphere (), is the worldwide sum of all ecosystems. It can also be termed the zone of life on the Earth. The biosphere (which is technically a spherical shell) is virtually a closed system with regard to mat ...

due to repeated nuclear detonations of increasing yield. Project SUNSHINE sought to measure the global dispersion of Sr-90 by measuring its concentration in the tissues and bones of the dead. Of particular interest was tissue from the young, whose developing bones have the highest propensity to accumulate Sr-90 and thus the highest susceptibility to radiation damage. SUNSHINE elicited a great deal of controversy when it was revealed that many of the remains sampled were utilized without prior permission from the deceased or from relatives of the dead, which wasn't known until many years later. The seminal contribution of Pecher on the therapeutic use of ⁸⁹Sr was “rediscovered” in the United States in 1976 by Marshall Brucer, former Chairman of the Medical Division of

Oak Ridge Institute of Nuclear Studies Oak Ridge Associated Universities (ORAU) is a consortium of American universities headquartered in Oak Ridge, Tennessee, with offices in Arvada, Colorado and Cincinnati, Ohio and staff at other locations across the country. History The organiza ...

. In 1973, two German physicians Nosrat Firusian and Carl G. Schmidt rediscovered, independently from Pecher's work, the therapeutic use of ⁸⁹Sr for the treatment of incurable pain in patients with neoplastic osseous infiltrations. Although not citing Pecher's work, Firusian and Schmidt referred to a 1950 article of John Lawrence and Robert H. Wasserman, in which they stated that "Radioactive strontium has been shown to behave similarly to calcium in the body" citing a 1941 paper of Pecher. This palliative treatment for breast and prostate cancers metastatic to the bones was only approved by the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

in 1993 for use in the US under the commercial name "Metastron", in the form of injectable Strontium Chloride, produced by Amersham International and became the first bone-seeking radiopharmaceutical that came into widespread use. Before leaving for Canada, Pecher filled a patent for a method of transmitting secret messages with radioactive invisible ink.

Biography

Work

References

Further reading