The Historical Origins of Nuclear Medicine and PET...discovery to the world. •14 February 1896, four days after news of the discovery reached the U.S, x-rays were used ... •1973

The Historical Origins of

Nuclear Medicine and PET

Tim Marshel R.T.

(R)(N)(CT)(MR)(NCT)(PET)(CNMT)

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SNMTS Approved

45-Hour PET Registry Review Course

The Historical Origins of Nuclear Medicine and PET• SNM Voice Reference Number: 028600, .5 CEH’s

• Participants must answer at least an 80% of the post-test questions correctly in order to receive CE credit.

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Program Objectives:

• Upon completion of this section, the student should be able to

discuss the founders and the events that marked the historic

beginning of the science of Nuclear Medicine and PET.

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In The Beginning ...

• On 8 November 1895, William Conrad Roentgen

discovered the x-ray.

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The First X-Ray

On 22 December 1895, Mr.

Roentgen made the first x-ray

photograph (Mrs. Roentgen’s

hand).

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The Aftermath• On 1 January 1896, Roentgen announced his

discovery to the world.

• 14 February 1896, four days after news of the discovery reached the U.S, x-rays were used

to guide surgery in New York.

• In early 1896, the Italian military began using x-rays to diagnose and treat wounded

soldiers

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At the same time ...

• In February 1896, Henri Becquerel discovered radioactivity.

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Historical Timeline

• Nuclear Medicine

• PET/CT Imaging

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Origins of Nuclear Medicine

• 1895 Wilhelm Roentgen discovers x-rays

• 1896 Henri Becquerel discovered mysterious "rays" from uranium.

• 1897 Marie Curie named the mysterious rays "radioactivity."

• 1901 Henri Alexandre Danlos and Eugene Bloch placed radium in contact with a tuberculous skin lesion.

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• 1903 Alexander Graham Bell suggested placing sources containing radium in or near tumors.

• 1913 Frederick Proescher published the first study on the intravenous injection of radium for therapy of various diseases.

• 1924 Georg de Hevesy, J.A. Christiansen and Sven Lomholt performed the first radiotracer (lead-210 and bismuth-210) studies in animals.


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• 1936 John H. Lawrence, the brother of Ernest, made the first clinical therapeutic application of an artificial radionuclide when he used phosphorus-32 to treat leukemia.

• 1942 Enrico Fermi and his associates demonstrated the first controlled chain reaction under the bleachers at Stagg Field at the University of Chicago.


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• 1951 The U.S. Food and Drug Administration (FDA) approved sodium iodide 1-131 for use with thyroid patients. It was the first FDA-approved radiopharmaceutical.

• 1951 Benedict Cassen, Lawrence Curtis, Clifton Reed and Raymond Libby automated a scintillation detector to "scan" the distribution of radioiodine within the thyroid gland.


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• 1957 W.D. Tucker's group at the Brookhaven National Laboratory invented the iodine-132 and technetium-99m generator, making these short-lived radionuclides available at distant sites from the production of the parent radionuclides.

• 1958 Hal Anger invented the "scintillation camera," an imaging device that made it possible to

conduct dynamic studies.


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• 1959 Berson and Yalow invented the technique of radioimmunoassay to detect insulin antibodies in human serum.

• 1959 Picker X-Ray Company delivered the first 3-inch rectilinear scanner.

• 1960 Louis G. Stang, Jr., and Powell (Jim) Richards advertised technetium-99m and other generators for sale by Brookhaven National Laboratory. Technetium-99m had not yet been used in nuclear medicine


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• 1961 Allis-Chalmers installed the first U.S. "medical center" cyclotron at Washington University Medical School. The cyclotron was designed by M.M. Ter-

Pogossian. • 1962 David Kuhl introduced emission reconstruction

tomography. This method later became known as SPECT and PET. It was extended in radiology to transmission X-ray scanning, known as CT.


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• 1962 John Kuranz, Nuclear Chicago, delivered the first commercial Anger camera to William Myers at Ohio State University.

• 1963 Henry Wagner first used radiolabeled albumin aggregates for imaging lung perfusion in normal persons and patients with pulmonary embolism.

• 1964 Paul Harper and Katherine Lathrup developed radiotracers labeled with Tc-99m for the study of brain, thyroid and liver.


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• 1970 W. Eckelman and P. Richards developed Tc-99m "instant kit" radiopharmaceuticals. The first one was Tc-99m-DTPA.

• 1971 The American Medical Association officially recognized nuclear medicine as a medical speciality.

• 1973 H. William Strauss introduced the

exercise stress-test myocardial scan.

• 1973 Elliot Lebowitz introduced thallium-201 for myocardial perfusion imaging, first proposed by Kawana.


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• 1976 John Keyes developed the first general purpose single photo emission computed tomography (SPECT) camera. Ronald Jaszczak developed the first dedicated head SPECT camera.

• 1977 The FDA required manufacturers to obtain an approved new drug application for new and existing radiopharmaceuticals. The requirements are essentially the same as those for other prescription drugs.


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• 1983 Henry Wagner carried out the first successful PET imaging of a neuroreceptor using himself as the experimental subject.

• 1990 Loyola University Nuclear Information System (LUNIS), the first educational worldwide interactive computer network for nuclear medicine, went on line.

• 1995 ADAC Laboratories shipped the first SPECT camera to offer coincidence detection capable of

FDG/PET imaging.


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• 1999 Sentinel node studies approved by HCFA for improved diagnosis and management of cancers.

• 2000 Time Magazine recognizes Siemens Biograph as the invention of the year.

• 2001 16.9 million nuclear medicine procedures were performed in the United States.


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The History of PET/CT Imaging

• PET/CT History

• Invented by Dr. Ron Nutt and Dr. David Townsend, the PET/CT scanner was named the Invention of the Year in 2000 by Time Magazine. In 2001, PET/CT was named Product of the Year by Frost and Sullivan.

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The first generation of PET/CT scanners included

a single slice spiral CT integrated with a PET

camera which utilized BGO detectors. Today, the

configurations have changed dramatically. You

can now select between a dual slice CT scanner

integrated with a high-end, high-throughput PET

camera incorporating the new and much faster

LSO crystals; or you may select a clinically

advanced 16 row CT scanner integrated with the

same high-end LSO PET system.

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Some of the early systems required two

consoles to operate the system, one for the CT

and one for the PET, and some of them

incorporated a patient bore size that started

at 70 cm for the CT and tapered to about 59

cm for the PET system. These types of systems

were not patient friendly, and also would not

allow for easy adaptation for radiation therapy

planning due to the inconsistent patient bore

size.

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Today, nearly all vendors have overcome these

shortcomings and now offer a variety of multi-

slice CT configurations. All systems are typically

operated from one control console and have a

consistent 70 cm bore which can accommodate

RT pallets and provide better patient comfort.

The industry has made great strides in a short

time to better serve the PET/CT market.

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The past 20 years have seen significant

advances in the development of

imaging instrumentation for PET.

Current high-performance clinical PET

scanners comprise more than 20,000

individual detector elements, with an

axial coverage of 16 cm and around

15% energy resolution. Can you identify

the most important factors that have

contributed to this remarkable

development in PET?

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This impressive progress is due essentially to

developments in detector construction, new

scintillators, better scanner designs, improved

reconstruction algorithms, high-performance

electronics and, of course, the vast increase in

computer power, all of which have been achieved

without an appreciable increase in the selling price

of the scanners.

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The PET/CT image is one of the most exciting

developments in nuclear medicine and

radiology, its significance being the merging

not simply of images but of the imaging

technology. Why is the recent appearance of

combined PET and CT scanners that can

simultaneously image both anatomy and

function of particular importance?

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Initial diagnosis and staging of tumours are

commonly based on morphological changes seen

on CT scans. However, PET can differentiate

malignant tissue from benign tissue and is a more

effective tool than CT in the search for

metastases. Clearly, valuable information can be

found in both, and by merging the two it is

possible now to view morphological and

physiological information in one fused image.

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To acquire the PET/CT image, a patient

passes through the CT portion of the

scanner first and then through the PET

scanner where the metabolic information

is acquired. When the patient has passed

through both portions, a merged or fused

image can be created.

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One of the first suggestions to use positron-emitting tracers

for medical applications was made in 1951 by W H Sweet

and G Brownell at Massachusetts General Hospital, and

some attempts were made to explore the use of positron-

emitting tracers for medical applications in the 1950s.

During the late 1950s and 1960s, attempts were made to

build a positron scanner, although these attempts were not

very successful. After the invention of the CT scanner in

1972, tomography in nuclear medicine received more

attention, and during the 1970s a number of different

groups attempted to design and construct a positron

scanner.

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S Rankowitz and J S Robertson of Brookhaven National

Laboratory built the first ring tomograph in 1962. In 1975,

M Ter-Pogossian, M E Phelps and E Hoffman at Washington

University in St Louis presented their first PET tomograph,

known as Positron Emission Transaxial Tomograph I (PETT

I). Later the name was changed to PET, because the

transaxial plane was not the only plane in which images

could be reconstructed. In 1979, G N Hounsfield and A M

Cormack were awarded the Nobel Prize for Physiology and

Medicine in recognition of their development of X-ray CT.

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Since the very early development of nuclear-

medicine instrumentation, scintillators such as

sodium iodide (NaI) have formed the basis for

the detector systems. The detector material

used in PET is the determining factor in the

sensitivity, the image resolution and the count-

rate capability.

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The only detector of choice in the mid-1970s was

thallium-activated NaI - NaI(Tl) - which requires care

when manufactured because of its hygroscopic

nature. More importantly, it also has a low density

and a low effective atomic number that limits the

stopping power and efficiency to detect the 511 keV

gamma rays from positron annihilation. Which other

scintillators have contributed to modern PET

tomography?

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Thanks to its characteristics, bismuth

germanate, or BGO, is the crystal that has

served the PET community well since the late

1970s, and it has been used in the fabrication of

most PET tomographs for the past two decades.

The first actual tomograph constructed that

employed BGO was designed and built by Chris

Thompson and co-workers at the Neurological

Institute in Montreal in 1978.

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Although the characteristics of BGO are good, a new

scintillator, lutetium oxyorthosilicate (LSO) (discovered by C

Melcher, now at CTI Molecular Imaging in Knoxville, TN), is a

significant advance for PET imaging. BGO is very dense but

has only 15% of the light output of NaI(Tl). LSO has a slightly

greater density and a slightly lower effective atomic number,

but has five times more light output and is seven times faster

than BGO. The first LSO PET tomograph, the MicroPET for

small animal imaging, was designed at the University of

California in Los Angeles (UCLA) by Simon Cherry and co-

workers. The first human LSO tomograph, designed for high-

resolution brain imaging, was built by CPS Innovations in

Knoxville, TN, and delivered to the Max Planck Institute in

February 1999.

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Documents

The Historical Origins of Nuclear Medicine and PET...discovery to the world. •14 February 1896, four days after news of the discovery reached the U.S, x-rays were used ... •1973