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Charles Pecher

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Charles Pecher
Born(1913-11-26)26 November 1913
Antwerp, Belgium
Died28 August 1941(1941-08-28) (aged 27)
Joliette, Canada
CitizenshipBelgium
Alma materUniversité libre de Bruxelles
Known forNuclear medicine

Charles Pecher (26 November 1913 – 28 August 1941) was a Belgian pioneer in nuclear medicine. He discovered and introduced strontium-89 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 autoradiographies of animals or organs after administration of strontium-89 or phosphorus-32 started the development of bone scintigraphy.

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

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Born in Antwerp on 26 November 1913, Pecher was the son of the liberal politician Édouard Pecher and Emilie Speth.[1] 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, where he specialized in biophysics. Pecher pioneered in fundamental neurophysiology through his evidence of random processes in the nervous system.[2][3][4] 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 to continue his research in the United States.[1] 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 and George Kistiakowsky. In 1940, he was appointed Research Fellow in the Radiation Laboratory at the University of California, Berkeley.

After two intense years, Pecher became entangled in the Second World War. In 1940 the Belgian Government in exile decided to raise a military unit from pre-war Belgian émigrés and soldiers rescued from Dunkirk and called up all Belgian nationals worldwide to join the Free Belgian Forces.[5] A battalion was formed in Canada from Belgian émigrés in the Americas.[6]

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.[7] In the end, Pecher responded to his convocation for the Belgian army in the United Kingdom. In Joliette, 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.[7] His daughter Evelyne was born two months later.

Work

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60-inch cyclotron at the University of California Lawrence Radiation Laboratory, Berkeley, in August, 1939

Between 1938 and 1940, Ernest O. Lawrence 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.[8] It was housed in the Crocker Laboratory. In 1940, Pecher was appointed Research Fellow in the Radiation Laboratory of Ernest O. Lawrence at the University of California, Berkeley, where he produced radioisotopes in the cyclotron under the supervision of John H. Lawrence and used them as radioactive tracers.[9][10]

The bones are largely composed of calcium and phosphorus in the form of tricalcium phosphate. 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 tissues.[11][12] For this reason, the metabolism of calcium attracted very early the interest of physicians looking for applying radioisotopes of calcium for therapeutic purposes.[13][14]

Pecher predicted and then demonstrated that strontium, which belongs to the same group in the periodic table, was absorbed by the human body in a manner similar to calcium.[15][16][17]

His work with strontium-89, a calcium analogue, eventually led to its administration to a terminal patient with osteoblastic metastases from a metastatic carcinoma of the prostate.[12][18][19][20] A posthumously published autoradiography of an amputated leg with strontium-89 is the first human bone scintigraphy.[18] It was the third medical radioisotope, after phosphorus-32 and iodine-131 introduced respectively by John H. Lawrence and Joseph G. Hamilton.[21][22][23] Pecher demonstrated using two cows the Sr-89 transfer to milk.[15] Pecher filed a patent in May 1941 for the synthesis of strontium-89 and yttrium-86 using cyclotrons and described the use of strontium for therapeutic uses .[24] The groundbreaking work of Pecher was forgotten for decades due to the classification of information linked to the Manhattan project and the American nuclear weapons program.[25][26][27][28][29][30][31] While 89Sr with a half-life of 50.6 days is used to treat bone cancer, 90Sr is an isotope of concern, with a half-life of 28.90 years, following a fallout from nuclear weapons and nuclear accidents as it's a common fission product. Its presence in bones can cause bone cancer, cancer of nearby tissues, and leukemia.[32]

United States Atomic Energy Commission commissioned in 1949 an investigation, codenamed Project GABRIEL, to gauge the impact of radioactive fallout resulting from nuclear warfare. It surmised that the radioactive isotope strontium-90 (Sr-90) represented the most serious threat to human health from nuclear fallout.[33] This resulted in the commissioning of Project SUNSHINE, which sought to examine the long-term effects of nuclear radiation on the biosphere due to repeated nuclear detonations of increasing yield.[34] 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.[34] 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.[35]

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.[23][36][37] 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.[38][39][40] 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.[12][41]

This palliative treatment for breast and prostate cancers metastatic to the bones was only approved by the Food and Drug Administration 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.[42][43][44][45][46]

Before leaving for Canada, Pecher filled a patent for a method of transmitting secret messages with radioactive invisible ink.[47]

References

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  1. ^ a b Lawrence, John H. (1941-12-05). "Charles Pecher". Science. 94 (2449): 533. Bibcode:1941Sci....94..533L. doi:10.1126/science.94.2449.533. ISSN 0036-8075. PMID 17756655.
  2. ^ Pecher, Charles (1939). "La Fluctuation D'excitabilité de la Fibre Nerveuse" (PDF). Archives Internationales de Physiologie. 49 (2): 129–152. doi:10.3109/13813453909150818. ISSN 0301-4541.
  3. ^ Pecher, Charles (1936). "Étude statistique des variations spontanées de l'excitabilité d'une fibre nerveuse". Comptes Rendus des Séances de la Société de Biologie. 122: 87–91.
  4. ^ Pecher, Charles (1937). "Fluctuations indépendantes de l'excitabilité de deux fibres d'un même nerf". Comptes Rendus des Séances de la Société de Biologie. 124: 839–842.
  5. ^ Baete, Hubert, ed. (1994). Belgian Forces in United Kingdom. Ostend: Defence. p. 24.
  6. ^ Thomas, Nigel (1991). Foreign Volunteers of the Allied Forces, 1939–45. London: Osprey. pp. 15–6. ISBN 978-1-85532-136-6.
  7. ^ a b Pecher, Evelyne (2011). Mon père Charles Pecher : l'homme de sciences : 1913–1941 : avec en annexe "The story in English" ... the scientist, World War II, the forgotten pioneer (in French). Bruxelles: Didier Devillez Éditeur. ISBN 9782873961329.
  8. ^ Schmor, Paul (2011). "Review of Cyclotrons for the Production of Radioactive Isotopes for Medical and Industrial Applications" (PDF). Reviews of Accelerator Science and Technology. 04 (1): 103–116. Bibcode:2011rast.book..103S. doi:10.1142/s1793626811000574. ISSN 1793-6268.
  9. ^ Helmholz, A. C.; Pecher, Charles; Stout, Perry R. (1941-06-01). "Radioactive Rb from Deuteron Bombardment of Sr". Physical Review. 59 (11): 902. Bibcode:1941PhRv...59..902H. doi:10.1103/PhysRev.59.902.
  10. ^ Pecher, Charles (1940). "A Long-Lived Isotope of Yttrium". Physical Review. 58 (9): 843. Bibcode:1940PhRv...58..843P. doi:10.1103/PhysRev.58.843.
  11. ^ Campbell, W. Wesley; Greenberg, David M. (1940). "Studies in Calcium Metabolism with the Aid of Its Induced Radioactive Isotope: I". Proceedings of the National Academy of Sciences. 26 (3): 176–180. Bibcode:1940PNAS...26..176C. doi:10.1073/pnas.26.3.176. ISSN 0027-8424. PMC 1078028. PMID 16588334.
  12. ^ a b c Pecher, Charles (1941). "Biological Investigations with Radioactive Calcium and Strontium". Proceedings of the Society for Experimental Biology and Medicine. 46 (1): 86–91. doi:10.3181/00379727-46-11899. ISSN 0037-9727. S2CID 88173163.
  13. ^ Bronner, F.; Aubert, J.-P.; Richelle, L. J.; Saville, P. D.; Nicholas, J. A.; Cobb, J. R. (1963). "Strontium and ITS Relation to Calcium Metabolism". Journal of Clinical Investigation. 42 (7): 1095–1104. doi:10.1172/JCI104795. ISSN 0021-9738. PMC 289378. PMID 14015769.
  14. ^ Cabrera, Walter E.; Schrooten, Iris; De Broe, Marc E.; D'Haese, Patrick C. (1999). "Strontium and Bone". Journal of Bone and Mineral Research. 14 (5): 661–668. doi:10.1359/jbmr.1999.14.5.661. ISSN 0884-0431. PMID 10320513.
  15. ^ a b Erf, L. A.; Pecher, Charles (1940). "Secretion of Radio-Strontium in Milk of Two Cows Following Intravenous Administration". Proceedings of the Society for Experimental Biology and Medicine. 45 (3): 762–764. doi:10.3181/00379727-45-11825P. ISSN 0037-9727. S2CID 83664224.
  16. ^ Pecher, Charles; Pecher, Jacqueline (1941). "Radio-Calcium and Radio-Strontium Metabolism in Pregnant Mice". Proceedings of the Society for Experimental Biology and Medicine. 46 (1): 91–94. doi:10.3181/00379727-46-11900. ISSN 0037-9727. S2CID 85342914.
  17. ^ Low-Beer, Bertram V. A.; Lawrence, John H.; Stone, Robert S. (1942). "The Therapeutic Use of Artificially Produced Radioactive Substances". Radiology. 39 (5): 573–597. doi:10.1148/39.5.573. ISSN 0033-8419.
  18. ^ a b Pecher, Charles (1942). Biological investigations with radioactive calcium and strontium; preliminary report on the use of radioactive strontium in the treatment of metastatic bone cancer. Vol. 2. University of California Publications in Pharmacology. pp. 117–150. OCLC 7837554.
  19. ^ Lawrence, J. H.; Hamilton, J. G.; Erf, L. A.; Pecher, Charles (1941). "Recent Advances in Clinical Medicine with the Aid of Artificially Prepared Radioactive Isotopes". Journal of Clinical Investigation. 20 (4): 436. doi:10.1172/JCI101239. ISSN 0021-9738. PMC 435076.
  20. ^ Pecher, Charles (1941). "Biological Investigations with Radioactive Calcium and Radioactive Strontium. Simultaneous Production of Radio-Strontium for Therapeutic Bone Irradiation and a Radio-Yttrium Suitable for Metallic Radiography". Journal of Applied Physics. 12 (4): 318–319. doi:10.1063/1.1712911. ISSN 0021-8979.
  21. ^ Lawrence, John H. (1979). "Early Experiences in Nuclear Medicine". Journal of Nuclear Medicine. 20 (6): 561–564. ISSN 0161-5505. PMID 13309834.
  22. ^ Hamilton, Joseph G.; Soley, Mayo H. (1939). "Studies In Iodine Metabolism by the Use of a New Radioactive Isotope of Iodine". American Journal of Physiology. 127 (3): 557–572. doi:10.1152/ajplegacy.1939.127.3.557. ISSN 0002-9513.
  23. ^ a b Brucer, Marshall (1976). "A History of Bone Scanning I – The first generation". Vignettes in Nuclear Medicine. 81.
  24. ^ US 2302470, Pecher, Charles, "Material and method for radiography", published 1941-05-14 
  25. ^ Bernstein, Barton J. (1985). "Radiological warfare: the path not taken". Bulletin of the Atomic Scientists. 41 (4): 44–49. Bibcode:1985BuAtS..41g..44B. doi:10.1080/00963402.1985.11455998.
  26. ^ Bruheze, Adri De La (1992). "Radiological Weapons and Radioactive Waste in the United States: Insiders' and Outsiders' Views, 1941-55". The British Journal for the History of Science. 25 (2): 207–227. doi:10.1017/s0007087400028776. JSTOR 4027299. PMID 11612822.
  27. ^ Hicks, Rodney J. (2016), "Back to the Future: Nuclear Medicine Rediscovers its Therapeutic Roots", Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy, Springer Japan, pp. 277–287, doi:10.1007/978-4-431-55894-1_21, ISBN 9784431558927
  28. ^ Brucer, Marshall (1990-09-01). A Chronology of Nuclear Medicine (First ed.). St. Louis, Mo.: Robert R Butaine. ISBN 978-0-9625674-0-7.
  29. ^ Finkel, Miriam Posner (1947). "The Transmission of Radio-Strontium and Plutonium from Mother to Offspring in Laboratory Animals". Physiological Zoology. 20 (4): 405–421. doi:10.1086/physzool.20.4.30151970. ISSN 0031-935X. PMID 18921410. S2CID 39714428.
  30. ^ Tutt, Margarett; Vaughan, J. M. (1949). "Metabolism of Radioactive Strontium in the Rabbit". The Biochemical Journal. 44 (4): xxix–xliii. doi:10.1042/bj044xxix. ISSN 0264-6021. PMC 1274900. PMID 16748556.
  31. ^ Kidman, Barbara; Tutt, Margaret L.; Vaughan, Janet M. (1950). "The retention and excretion of radioactive strontium and yttrium (Sr89, Sr90 and Y90) in the healthy rabbit". The Journal of Pathology and Bacteriology. 62 (2): 209–227. doi:10.1002/path.1700620208. ISSN 0368-3494. PMID 15437247.
  32. ^ "Strontium – Radiation Protection". EPA. 2017. Retrieved 18 June 2012.
  33. ^ "Report on Project GABRIEL". U.S. ATOMIC ENERGY COMMISSION Division of Biology and Medicine. July 1954. Archived from the original on 2011-02-12. Retrieved 2011-02-25.
  34. ^ a b "Worldwide Effects of Atomic Weapons: Project SUNSHINE" (PDF). Retrieved 2010-07-10.
  35. ^ PROJECT SUNSHINE AND THE SLIPPERY SLOPE Centre for Medical Education Dundee University Medical School Sue Rabbitt Roff
  36. ^ Robinson, Ralph G.; Spicer, Jay A.; Preston, David F.; Wegst, Audrey V.; Martin, Norman L. (1987). "Treatment of metastatic bone pain with strontium-89". International Journal of Radiation Applications and Instrumentation. Part B, Nuclear Medicine and Biology. 14 (3): 219–222. doi:10.1016/0883-2897(87)90045-6. ISSN 0883-2897. PMID 3667305.
  37. ^ Robinson, R G; Blake, G M; Preston, D F; McEwan, A J; Spicer, J A; Martin, N L; Wegst, A V; Ackery, D M (1989). "Strontium-89: treatment results and kinetics in patients with painful metastatic prostate and breast cancer in bone". RadioGraphics. 9 (2): 271–281. doi:10.1148/radiographics.9.2.2467331. ISSN 0271-5333. PMID 2467331.
  38. ^ Firusian, Nosrat; Schmidt, Carl G. (1973). "Neue Methode zur Behandlung inkurabler Schmerzzustände bei neoplastischer ossärer Infiltration" [Radioactive strontium for treating incurable pain in skeletal neoplasms]. Deutsche Medizinische Wochenschrift (in German). 98 (49): 2347–2351. doi:10.1055/s-0028-1107254. ISSN 0012-0472. PMID 4763877.
  39. ^ Firusian, Nosrat (1974). "Kinetik des Radiostrontium". Nuklearmedizin (in German). 13 (2): 127–138. doi:10.1055/s-0038-1624849. ISSN 0029-5566.
  40. ^ Firusian, Nosrat; Mellin, Paul; Schmidt, Carl G. (1976). "Results of 89 Strontium Therapy in Patients with Carcinoma of the Prostate and Incurable Pain from Bone Metastases: A Preliminary Report". The Journal of Urology. 116 (6): 764–768. doi:10.1016/S0022-5347(17)59002-3. ISSN 0022-5347. PMID 1003647.
  41. ^ Lawrence, John; Wasserman, Robert L. (1950). "Multiple Myeloma: A Study of 24 Patients Treated With Radioactive Isotopes (Phosphorus-32 And Strontium-89)" (PDF). Annals of Internal Medicine. 33 (1): 41–55. doi:10.7326/0003-4819-33-1-41. PMID 15426091.
  42. ^ "Amersham International Celebrates Its Fiftieth Birthday". European Journal of Nuclear Medicine. 17 (6–8): 374–380. 1990. doi:10.1007/bf01268031. ISSN 0340-6997. S2CID 1722663.
  43. ^ Laing, A. H.; Ackery, D. M.; Bayly, R. J.; Buchanan, R. B.; Lewington, V. J.; McEwan, A. J. B.; Macleod, P. M.; Zivanovic, M. A. (1991). "Strontium-89 chloride for pain palliation in prostatic skeletal malignancy". The British Journal of Radiology. 64 (765): 816–822. doi:10.1259/0007-1285-64-765-816. ISSN 0007-1285. PMID 1717094.
  44. ^ Lewington, Valerie J.; McEwan, Alexander J.; Ackery, Duncan M.; Bayly, Russell J.; Keeling, David H.; Macleod, Patricia M.; Porter, Arthur T.; Zivanovic, Maureen A. (1991). "A prospective, randomised double-blind crossover study to examine the efficacy of strontium-89 in pain palliation in patients with advanced prostate cancer metastatic to bone". European Journal of Cancer and Clinical Oncology. 27 (8): 954–958. doi:10.1016/0277-5379(91)90257-e. ISSN 0277-5379. PMID 1716935.
  45. ^ Bauman, Glenn; Charette, Manya; Reid, Robert; Sathya, Jinka (2005). "Radiopharmaceuticals for the palliation of painful bone metastases – a systematic review". Radiotherapy and Oncology. 75 (3): 258.E1–258.E13. doi:10.1016/j.radonc.2005.03.003. PMID 16299924.
  46. ^ Lee, C. K.; Aeppli, D. M.; Unger, J.; Boudreau, R. J.; Levitt, S. H. (1996). "Strontium-89 chloride (Metastron) for palliative treatment of bony metastases. The University of Minnesota experience". American Journal of Clinical Oncology. 19 (2): 102–107. doi:10.1097/00000421-199604000-00003. ISSN 0277-3732. PMID 8610630.
  47. ^ US 2407381, Pecher, Charles, "Means and method for transmitting secret intelligence", published 1946-09-10 

Further reading

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