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March 16, 2021 Tuesday 11:20:54 AM IST

Versatility of Nuclear Medicine

Health Monitor

Nuclear Medicine is traditionally defined as a field of medicine, where clinically approved radionuclides / radioisotopes tagged with specific biological molecules are used, for the diagnosis and treatment of clinical conditions. Unlike X-ray or CT imaging, which provide exquisite anatomical details of the body, nuclear medicine imaging, is inherently a functional imaging modality, providing information about the functional status (either physiological or pathological) of the organ / organ system being studied. Further, the therapeutic application of radioisotopes (endoradiotherapy), for malignant as well as certain benign conditions (the most successful example being thyroid disorders), have paved the way for Nuclear Medicine to grow and establish itself as an independent and rapidly progressing medical discipline.

Isotopes, as we have learnt in primary school, are variants of any particular chemical element, which have the same atomic number but different atomic weight. Some isotopes of elements contain an unstable configuration of protons and neutrons in their atomic nucleus, and emit this excess energy in the form of gamma (γrays) and/or particulate [alpha (α) or beta (β)] radiation, to achieve stable status. These are called radioisotopes, and they may be naturally occurring or artificially created. Gamma emissions are used for diagnostic imaging as they are capable of traversing through the human body, while particulate emissions are used primarily for targeted therapy.

Radioisotopes, Radiopharmaceuticals

Clinical use of radioisotopes is approved and monitored by the Atomic Energy Regulatory Board (AERB) of India, in accordance with guidelines set by the International Atomic Energy Agency (IAEA). The primary guiding principle being ‘As Low as Reasonably Achievable’ (ALARA), to keep the radiation exposure of both the patients as personnel well within permissible limits. Some Nuclear Medicine procedures are routinely performed even in infants, and the only absolute contraindication is pregnancy.


Radiopharmaceuticals (RPs) may be seen as an entity comprising of a clinically approved radioisotope bound to biomolecules engineered to specifically target a particular organ / organ system in the body. They are administered orally, intravenously or sometimes directly into the lesion. Radiopharmaceutical chemistry and research is steadily evolving into a multidisciplinary field involving radiochemists, biologists, physicists, mathematicians, engineers and clinicians scientists.Rapid advancements are being made in radioisotope production and synthesis of noveltracers for the next generation of molecular targets. 

Nuclear Medicine Imaging

Nuclear Medicine Imaging or Nuclear Scintigraphy or Gamma scan,has indeed come a long way since its humble beginnings as a single probe moving in a rectilinear fashion and producing vague 2-dimentional (2D) images of the radiopharmaceutical within the body; to the current multidetector systems which can provide 3D and 4D information. Gamma Camera or SPECT (Single Photon Emission Computed Tomography) and the Positron Emission Computed Tomography (PET) constitute theprimary imaging techniques used in a Nuclear Medicine department.

Planar (static / cine images) and tomographic images on SPECT systems using 99mTechnetium (99m-Tc) or 131Iodine (131-I) based radiopharmaceuticals, have been the mainstay in many Nuclear Medicine departments. Image processing algorithms based on tracer kinetic principles allow the quantification of function in the organs of interest. Some of the routine applications for SPECT imaging include assessing salivary gland function, localizing epileptogenic focus in brain, evaluating thyroid gland function or locating hyperfunctioning parathyroid glands, assessing the myocardium for any past or impending coronary events, evaluating the functional capacity of lungs, perfusion and function of native as well transplanted liver and kidneys, assessing the skeletal system for infection or malignancy, and evaluating lymphatic drainage of limbs or tumors.A few rarer scintigraphy procedures include salivagram, dacryoscintigraphy and 99m-Tc labeled RBC studies.


On the other hand, PET due to its unique physics has a significantly better resolution than SPECT imaging and has an innate ability for more accurate quantification. The introduction of the PET radiopharmaceutical 18-Fluorine (18-F) labeled fluorodeoxyglucose (FDG) has been a major game-changer in oncology and now FDG PET is possibly the most recognized Nuclear Medicine procedure among clinicians as well as the general public. FDG as the name suggests is glucose analogue, and when injected in the body, accumulates at sites showing a high metabolic activity. This is the principle behind its use to identify many malignancies, which tend to show higher metabolism (identified as abnormal foci of increased tracer uptake) in comparison to the surrounding normal tissue. No other 18-F labeled PET RPs approved for clinical use have been as popular as FDG.Standardized Uptake Value (SUV) is a PET quantification parameters, is a ubiquitous part of any PET report and has gained importance in clinical oncology. It basically represents the degree of metabolic activity in a lesion and has shown to have diagnostic and prognostic values, which may help guide therapy. However, if not used in the appropriate context and especially in the absence of an expert reader’s qualitative evaluation, the practical utility of SUVs could be highly questionable, produce superfluous information and possibly mislead.

Hybrid Imaging

The turn of the century witnessed one of the greatest milestones in Nuclear Medicine imaging - introduction of ‘Hybrid’ imaging. The inherent low contrast and low-resolution anatomy in PET (only) scans was insufficient for accurate localization of abnormal foci of PET tracer uptake. Therefore, the strengths of PET and CT were coupled to produce, precisely co-registered anatomical and functional images that can be acquired in a single scan session– the PET-CT scan.This was soon followed up with the inception of SPECT-CT imaging, which is gaining importance in endocrinology, oncology and musculoskeletal imaging. Besides anatomic localization, the CT component of these hybrid procedures is used for better attenuation correction of the PET and SPECT data, allowing better reconstruction techniques, and ultimately better image quality. The latest innovation has been the introduction of PET-MRI, which combines the functional imaging of PET with the anatomic and quantitative strengths of MRI.  PET-MRI is being effectively utilized for brain studies, exploiting its full potential for other clinical conditions is presently being evaluated.

Theranostics


Theranostics (Therapy + Diagnostics) refers to the close relationship between diagnostics and consequent therapy. In the Nuclear Medicine context it is used specifically for imaging and therapy using the same or 2 very similar radiopharmaceuticals. Though it’s considered a relatively new concept in clinics,the principle of theranostics has been used since decades in Nuclear Medicine, in the form of 131-I being used for imaging and therapy of benign and malignant thyroid diseases. Recently, theranostics has been successfully applied in the management of neuroendocrine tumors (NETs) and prostate cancer. This new revolution in Nuclear Medicine was accomplished with the genesis of the 68Galium (68-Ga) labeled ligands; PSMA (Prostate Specific Membrane Antigen – for prostate cancer) and DOTANOC (an Octreotide derivative – for neuroendocrine tumors). These ligands when labeled with 68-Ga, can be used as PET tracers for imaging. Additionally, the same ligands when labeled with α particleemitting radioisotope 225Actinium (225-Ac) or b particle emitting radioisotope177Lutetium (177-Lu), can be used for treatment of these conditions. Both these theranostic agents are now slowly being incorporated in routine oncology practice.

Inspired by their success, a slew of new theranostic approaches based on antibodies, peptidomimetics, and small molecule compounds are being investigated. A few promising candidates which have now entered human trials and even available in India are: 68-Ga FAPI (Fibroblast Activation Protein Inhibitors) which target tumor microenvironment. Some even predict FAPI to potentially challenge FDG as universal tumor tracer. 68-Ga Pentixafor which targets the overexpressed CXCR4 chemokine receptor in certain malignancies such as those of brain, breast, lung, pancreas, ovary and melanomas.  Theranostics has acquired greater importance in recent years due to theinitiation of precision oncology, which aims atprecisely targeting the molecular characteristics of tumors.

Precision Oncology

Precision oncology refers to profiling of tumors to identify molecular alterations which can then be specifically targeted during therapy. Discovery of EGFR (Epidermal Growth Factor) mutations in lung cancer which made the tumors susceptible to tyrosine kinase inhibitors (TKIs), heralded the precision oncology revolution. Huge investments are being made in genomics, epigenetics and proteomics (”omics”) of different tumors. This is critical for the future development of targeted therapies. However, these “omics” technologies tend to lack spatial information, both on the microscopic level (like intratumoral heterogeneity) as well as on a whole-patient level (location of metastatic deposits and heterogeneity among these deposits). Therefore, combining a functional imaging modality with “omics” technologies appears to be a necessary step in understanding and converting all this information into novel therapeutic strategies. Presently tracers such as 68-Ga labeled PD-L1 antibody are undergoing preclinical testing.


Looking ahead

Over the past decades, Nuclear Medicine has undergone some drastic changes. Diagnostic procedures, which were once considered fundamental to this discipline, have almost entirely been replaced by other modalities. While some techniques which were once thought to be exclusively for research purposes only, are now part of everyday clinical practice. This unpredictability is possibly be due to innate ability of this field to innovate and rapidly adapt to new scientific developments and clinical needs. The manner in which cancer is now being defined and treated is rapidly changing, and Nuclear Medicine seems to be taking a more central role in the same; at the level of preclinical research and well as at bed-side. Besides oncology, newer tracers and gamma imaging systems have made headways in the field of cardiology and neurology which are helping clinicians treat patients more confidently and successfully. There is an important role for members from every branch of science in Nuclear Medicine, and based on what we have witnessed this far, it is safe to say that the future of Nuclear Medicine is ‘scintillating’.



Dr. Vijay Harish Somasundaram

Consultant - Nuclear Medicine, Rajagiri Hospital Read more articles..
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