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 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 1  |  Issue : 1  |  Page : 26-32

Nuclear Medicine from the past to the present: A brief story of its development, key impact areas in current times and its potential for the future


1 Department of Nuclear Medicine, AIIMS, Rishikesh, Uttarakhand, India
2 Department of Orthopedics, AIIMS, Rishikesh, Uttarakhand, India
3 Radiation Medicine Centre, Bhabha Atomic Research Centre, Mumbai, Maharashtra, India

Date of Submission28-May-2020
Date of Decision15-Jun-2020
Date of Acceptance17-Jun-2020
Date of Web Publication20-Jul-2020

Correspondence Address:
Dr. Vandana Kumar Dhingra
Department of Nuclear Medicine, AIIMS, Rishikesh, Uttarakhand
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JME.JME_71_20

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  Abstract 


In this review, we briefly outline the journey and development of Nuclear Medicine in the Western world in contrast with its development in India and highlight the key areas where this modality has an impact today and likely to develop in the near future. A special mention of the recent developments in clinical Nuclear Medicine including Positron Emission Tomography-Computed Tomography (PET-CT) which form the backbone of personalised medicine is made.

Keywords: Nuclear Medicine, PET-CT, single-photon emission computed tomography/computed tomography, theranostics


How to cite this article:
Dhingra VK, Dhingra M, Basu S. Nuclear Medicine from the past to the present: A brief story of its development, key impact areas in current times and its potential for the future. J Med Evid 2020;1:26-32

How to cite this URL:
Dhingra VK, Dhingra M, Basu S. Nuclear Medicine from the past to the present: A brief story of its development, key impact areas in current times and its potential for the future. J Med Evid [serial online] 2020 [cited 2020 Aug 9];1:26-32. Available from: http://www.journaljme.org/text.asp?2020/1/1/26/290142




  Introduction and Historical Perspectives Top


Landmark events in the development of Nuclear Medicine in the Western world

George de Hevesy, known as the 'father of Nuclear Medicine'– first described the radiotracer principle that underpins the use of radionuclides and radiopharmaceuticals to investigate the behaviour of stable atoms and molecules. The 'tracer principle' states that 'radiopharmaceuticals' in minute quantities can be employed to probe the system and participate in biological processes but do not alter or perturb them.[1]

Despite its rapid developments, especially over the last two decades, Nuclear Medicine remains a rather lesser known speciality even after a seeming presence since more than 80 years of its history in clinical medicine. Nuclear Medicine has also been the speciality to introduce the concept of 'Theranostics' i.e., therapy with diagnostics (131 I for thyroid imaging [TI] and therapy being one of the first and successful examples of this principle).

One of the pioneering initial works on thyroid cancer with radioisotopes was done in the early 1940s, which showed that ablation of thyroid residual cells was necessary for the therapy of metastasis with radioiodine. This landmark work converted thyroid cancer from a terminal disease to a cancer with 85% overall survival rates.[2],[3],[4] A remarkable moment for the development of Nuclear Medicine was on 31 March 1941 when Dr Saul Hertz administered radioactive iodine to an Elizabeth D at the Massachusetts General Hospital. This was the first therapeutic procedure of radioactive iodine in clinical setting.[5]

The simultaneous discovery of diagnostic radioisotopes such as technetium-99m and instrumentation (Gamma Camera by Hal Anger) in the two decades from the 1950s led to the development of popular gamma camera-based diagnostic imaging in Nuclear Medicine. The most initial imaging was utilized for brain imaging and was nicknamed 'the hair dryer' because of its shape like the instruments used in salons.

Even though the first Positron Emission Tomography (PET) imaging instrument was developed in 1953 by Brownell and Sweet, PET imaging did not see much clinical potential up until the discovery of18 F-fluorodeoxyglucose (FDG) in 1975.[6],[7],[8],[9]

2-Deoxy-2-(18 F) fluoro-D-glucose – often abbreviated (18 F) FDG or simply FDG – is a radiolabeled form of glucose in which a fluorine-18 atom takes the place of a hydroxyl group. FDG was developed with the specific purpose of measuring glucose metabolism in the human brain. However, its utility in tumour diagnosis led to a revolutionary change in the management of cancers worldwide over the next two decades. The groundbreaking discovery of (18 F) FDG opened the doors to the exploration of a wide range of diseases and conditions, including drug addiction, eating disorders, attention deficit hyperactivity disorder, Alzheimer's disease, epilepsy and coronary artery disease. In its later course, (18 F) FDG-PET imaging has also fundamentally reshaped the diagnosis, staging, and treatment monitoring of cancer. Because tumour cells have high utilisation of glucose, (18 F) FDG-PET scans can pick up these as 'hotspots' from the surrounding healthy tissue, even before anatomical changes are detected with conventional imaging.

The development of hybrid imaging i.e., PET/computed tomography (CT) localising lesions by fusing the anatomical images, improved detectability and revolutionised imaging. Advances in radiochemistry for production and synthesis of new PET radioisotopes led to more and more use of PET/CT in the clinical setting over the last few decades. These combined advances brought Nuclear Medicine to the forefront in management of key areas in oncology, cardiology and neurology.

Developmental Milestones of Nuclear Medicine in India

In India, Dr Homi Jehangir Bhabha is considered to be the 'Father of the Indian Nuclear Program'. In a letter to Dr Jeejeebhoy on 7 August 1962 [Figure 1], the vision of Dr Homi Bhabha regarding the Nuclear Medicine programme in India is quite evident. With the establishment of major institutions such as Bhabha Atomic Research Centre and Institute of Nuclear Medicine and Allied Sciences, the Indian Nuclear Medicine programme took off in the 1960s and we can say that Nuclear Medicine was not much behind the Western counterparts historically. The first PET scanner was established at the Radiation Medicine Centre in Mumbai in 2002 followed by a series of PET scanners all over India in public and private sector.[10] The revolution in oncology management brought about by PET/CT has made the biggest impact in the development of the Nuclear Medicine speciality in India similar to the trend in the Western world. What is of significance is that this revolution has happened in India more or less simultaneous with the rest of the world unlike so many modalities which would come to our country one or two decades later than the Western world. This could be attributed to the simultaneous development of satellite-based communication (worldwide web), computing and overall development of India.
Figure 1: The Visionary: Dr Homi Bhabha's Letter to Dr Jeejeebhoy (source, wiki)

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  Advances in Nuclear Medicine over the Past Two Decades Top


The virtual flip-flop of gamma camera (single-photon emission computed tomography/computed tomography) and positron emission tomography/computed tomography applications: A worldwide trend

The thyroid, bone and cardiac scans are the most frequently performed conventional Nuclear Medicine procedures in descending order in recent times. With a marked increase of PET/CT and SPECT/CT, the number of conventional scintigraphy procedures is declining. Cardiac, lung and brain scans and lymphoscintigraphy are increasingly requested with a decline in bone and thyroid scan.

Among the conventional scintigraphy, the renal scintigraphy continues to be used very widely by urologists and paediatric surgeons; the common application of renal scintigraphy ranges from detection of upper outflow tract obstruction and assessment of renal transplant complication such as rejection, Acute tubular necrosis (ATN) and urinary leak to evaluation of healthy voluntary kidney donors.[11]

Bone scintigraphy was at one time a leading examination (32.3%), followed by myocardial scintigraphy (24.1%) and cerebral perfusion study (18.0%).

A recent study in Japan (which best represents both developed world and Asian counterpart) revealed an overall rise in SPECT examinations. It also showed an increase in PET/CT clinical use with nearly 90% in oncology and 98%18 F-FDG scans. Radioiodine was and continues to be used widely. Other therapies such as Ra-223 targeted therapy for carcinoma prostate were seen to be on the rise.[12]

These trends can be assumed to reflect the worldwide trend of a stable SPECT/CT exam, increasing PET/CT and Cyclotron installations and use, as well as rise in therapeutic Nuclear Medicine.

If we analyse the developments of Nuclear Medicine over the last two decades in India and also the rest of the world, we can divide the period into two halves – the first decade (2000–2010) witnessed developments primarily in molecular PET imaging, while the latter half (2010–present) marked the development of radionuclide therapy and theranostics and development of177 Lu-based therapies [Figure 2]. The use of targeted therapy in the form of radioisotopes is soon to make its mark in the era of precision medicine. Over the past decade, various agents have been FDA approved and many new agents are on the anvil.
Figure 2: Nuclear Medicine: Impact and progress areas in the past two decades

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An estimate of the popularity and growth of literature can be seen. The search engine PUBMED reveals around 55,000 articles on searching the word 'PET/CT', of which about 45,000 (81%) are published within the past 20 years, around 20,000 (36%) in the past 5 years and more than 35,000 (63%) articles in the past 5 and 10 years. This reflects the volume of work and the day-to-day development in clinical work on PET/CT.

Indications and utility of the gamma camera or SPECT/CT scanner are showing a worldwide decline over the past decade, with an exponential rise in indications as well as utility of PET/CT scans in Nuclear Medicine.

The advent of PET/magnetic resonance imaging (MRI) has also taken a front seat in the last few years of this decade. An addition to the hybrid imaging methods, PET/MRI offers the advantage of better contrast and resolution and lesser radiation exposure in comparison to PET/CT. Currently installed at limited centres worldwide, there is a growing trend for PET/MRI, and the common indications are listed in [Table 1].[13]
Table 1: Positron emission tomography/magnetic resonance imaging: Evolving clinical applications

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  Current Major Clinical Applications of Nuclear Medicine Imaging and Therapy Top


With a gamut of modalities available in Nuclear Medicine, it is important to highlight key areas of applications. [Table 1], [Table 2], [Table 3], [Table 4] are for the same, however this is not a complete list of procedures. To mention all procedures is beyond the scope of this text. In addition, there are various non-imaging modalities such as Red blood cells (RBC) survival studies and I-131 uptake test, which are also routinely performed at many centres.
Table 2: Gamma camera/single-photon emission computed tomography/computed tomography-based imaging

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Table 3: Positron emission tomography/computed tomography-based imaging and Key areas of clinical applications

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Table 4: Common therapeutic applications of Nuclear Medicine

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  Recommendations for Positron Emission Tomography/computed Tomography in Oncology Practice Top


18F FDG PET/CT being now strongly integrated in routine clinical oncology practice, it is imperative to have an understanding of the key areas where F-18 FDG PET/CT has major impact and the potential areas which require further clinical experience. [Table 5] provides the current recommendations for use of F-18 FDG PET/CT in oncology practice.[14]
Table 5: Recommendations for F-18 PET/CT in oncology practice

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  Theranostics and the Future of Imaging - the Concept of Molecular Imaging Reporting and Data Systems Top


The potential to perform imaging and therapy utilising the same molecule/basis is called theranostics. It is more of a “see what you treat” and “treat what your see” approach. Historically radioiodine imaging and therapy for differentiated thyroid cancer was one of the earliest proof-of-the concept examples of theranostics. In recent years, theranostics is redefining management of neuroendocrine tumours, prostate cancer and lymphomas and form important basis for personalised medicine. These modalities hold promising avenues in the management of various tumours in the future.

Recently, a futuristic system for reporting of Nuclear Medicine imaging (Molecular Imaging Reporting and Data Systems [MI-RADS] for theranostic applications) is being developed. MI-RADS is a system similar to its predecessors in the radiology arena (Breast Imaging-RADS, TI-RADS); the system for MI should convey to the reader the level of certainty that an equivocal finding is a site of disease, identify and navigate common pitfalls and artefacts, facilitate communication with clinicians and select/eliminate candidates for treatment with177 Lu-labelled compounds in a theranostic setting.[15]


  Concluding Remarks Top


Nuclear Medicine or Molecular Imaging (MI) is a unique modality, which reveals functional images on internal administration of small (tracer amounts) of radioisotopes. With a history of more than 80 years since its inception in medical science, this speciality has seen rapid progress. Advances in instrumentation in the form of hybrid imaging equipment (PET/ CT and SPECT/CT), advances in radiochemistry, theranostics approach of 'treat what you see' and 'see what you treat' along with the ever widening availability of this modality have led to a revolution in the management of most solid tumours and haemato oncology. It is making its impact on management in other clinical areas such as musculoskeletal diseases, infection and inflammations, paediatrics, endocrinology, neurology and cardiology.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Niese S. George de Hevesy (1885–1966): Founder of radioanalytical chemistry. Czech J Phys 2006;56 Suppl D:D3-11.  Back to cited text no. 1
    
2.
Keston AS, Ball RP, Frantz VK, Palmer WW. Storage of radioactive iodine in a metastasis from thyroid carcinoma. Science 1942;95:362-3.  Back to cited text no. 2
    
3.
Seidlin SM, Marinelli LD, Oshry E. Radioactive iodine therapy; effect on functioning metastases of adenocarcinoma of the thyroid. J Am Med Assoc 1946;132:838-47.  Back to cited text no. 3
    
4.
Luster M, Clarke SE, Dietlein M, Lassmann M, Lind P, Oyen WJ, et al. Guidelines for radioiodine therapy of differentiated thyroid cancer. Eur J Nucl Med Mol Imaging 2008;35:1941-59.  Back to cited text no. 4
    
5.
Hertz B. A tribute to Dr. Saul Hertz: The discovery of the medical uses of radioiodine. World J Nucl Med 2019;18:8-12.  Back to cited text no. 5
[PUBMED]  [Full text]  
6.
Nutt R. 1999 ICP distinguished scientist award. The history of positron emission tomography. Mol Imaging Biol 2002;4:11-26.  Back to cited text no. 6
    
7.
Brownell GL, Sweet WH. Localization of brain tumors. Nucleonics 1953;11:40-5.  Back to cited text no. 7
    
8.
Phelps ME, Hoffman EJ, Mullani NA, Ter-Pogossian MM. Application of annihilation coincidence detection to transaxial reconstruction tomography. J Nucl Med 1975;16:210-24.  Back to cited text no. 8
    
9.
Ter-Pogossian MM, Phelps ME, Hoffman EJ, Mullani NA. A positron-emission transaxial tomograph for nuclear imaging (PETT). Radiology 1975;114:89-98.  Back to cited text no. 9
    
10.
Sharma AR. Nuclear Medicine in India: A historical journey. Indian J Nucl Med 2018;33:S5-10.  Back to cited text no. 10
[PUBMED]  [Full text]  
11.
Archer KD, Bolus NE. Survey on the use of nuclear renal imaging in the United States. J Nucl Med Technol 2016;44:223-6.  Back to cited text no. 11
    
12.
Nishiyama Y, Kinuya S, Kato T, Kayano D, Sato S, Tashiro M, et al. Nuclear medicine practice in Japan: A report of the eighth nationwide survey in 2017. Ann Nucl Med 2019;33:725-32.  Back to cited text no. 12
    
13.
Vitor T, Martins KM, Ionescu TM, da Cunha ML, Baroni RH, Garcia MR, et al. PET/MRI: A novel hybrid imaging technique. Major clinical indications and preliminary experience in Brazil. Einstein (Sao Paulo) 2017;15:115-8. doi:10.1590/S1679-45082017MD3793.  Back to cited text no. 13
    
14.
Salaün PY, Abgral R, Malard O, Querellou-Lefranc S, Quere G, Wartski M, et al. Good clinical practice recommendations for the use of PET/CT in oncology. Eur J Nucl Med Mol Imaging 2020;47:28-50.  Back to cited text no. 14
    
15.
Werner RA, Thackeray JT, Pomper MG, Bengel FM, Gorin MA, Derlin T, et al. Recent Updates on Molecular Imaging Reporting and Data Systems (MI-RADS) for Theranostic Radiotracers-Navigating Pitfalls of SSTR- and PSMA-Targeted PET/CT. J Clin Med 2019 19;8:1060. doi: 10.3390/jcm8071060. PMID: 31331016; PMCID: PMC6678732  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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