Radionuclide imaging in surgery: part 2

Radio-nuclide imaging in surgery: Part 2
‰ S. Sanyal MS
‰ I. Nyaruhirira
Director,
Centre Hospitalier de KIGALI, "C.H.K."
Kigali, Rwanda.
From extracting natural radioactive substances from crude pitch blende ore to creating artificial radioactivity in
betatrons is a long leap indeed. In this treatise the authors tell us about the clinical applications
of one of the most versatile radioisotope, namely technetium.

With the discovery of radium from pitch blende, Mme Curie unlocked the secret of the atom. After a lifetime of work
with radioactivity her body got ravaged by its effects, but the value of knowledge she left behind is incalculable in
terms of benefits to mankind. Having dealt with the harmful and therapeutic effects of radioactivity (and ionising
radiation) in the December '98 issue of SURGERY, this issue focuses on the diagnostic applications of radioactivity.
Nuclear physics
The nucleus of a radioactive atom (radio-nuclide), consisting of protons and neutron(s) is in an unstable, high-energy
state which tends to revert back to a stable (basal) state (a phenomenon known as 'decaying') by releasing the excess
energy in the form of electromagnetic and/or corpuscular emission(s). This is the essence of radioactivity. All
elements with atomic number (AN) > 83 have this property and the same may be induced in all other known
elements. Thus radioactivity may be natural (viz. 235U, 40K) or artificial (viz. 60Co, 99mTc).
Emissions
These may be electromagnetic and/or corpuscular and all are ionising radiation. They may be produced by machines
also, as described in the previous issue. They may be; (a) heterogeneous (particles of various energies or of different
types, or photons of different frequencies and wavelengths); (b) homogeneous (mono-energetic particles of a single
type, or photons of extremely narrow frequency and wavelength); or (c) mono-energetic (all particles or photons
originate with and have the same energy).
Decay of heavy elements (226Radium, 222Radon) releases α particles (He2+), short-lived radio-arsenic emits positrons (e+), 32P emits pure β particles (e-), 99mTc and 125I emit only γ rays, 131I and 198Au (gold) give off mixed β particles and γ rays (table 1). Rearrangement of electrons in the inner shells of atoms, by the capture of an orbital electron by the nucleus during decay, produces x-rays. In mixed emissions one may predominate (198Au gives 0.411 Me V γ rays (6-10 % of total dose) and 0.96 Me V β particles). Radioisotopes
Isotopes are elements with same AN (number of protons or electrons) but different mass numbers (atomic weight;
AW) (number of protons and neutrons in the nucleus). The former is constant for an element and confers its chemical
characteristics. The variability of the latter (due to variations in the number of neutrons) gives rise to various
isotopes. The decimal in the AW indicates a mixture of isotopes (e.g. AW of K is 39.102, indicating a mixture of 39K
and 40K). The pre-superscript is the AW. One isotope may be stable and the other(s) radioactive (radioisotope). Of
the 9 isotopes of iodine (123, 125, 127, 130, 131, 132, etc) only 127I is stable. Again, the radioisotopes may be natural
or artificial (40K is natural, 42K is artificial). 99mTc (technetium) is an artificial radioisotope (it has no stable or natural
isotope). After decaying, a radioisotope may get converted to its stable form or to another element, which may be
stable or radioactive (e.g. 226Radium decays to 222Radon which is also radioactive). Conversely a stable isotope may
get converted into a radioisotope (infra).
Artificial (induced) radioactivity
This is produced by bombarding a stable element with high velocity particles (viz. α, β or neutrons) in a cyclotron or
a nuclear reactor. The stable nucleus acquires the excess energy and becomes radioactive. The mechanisms of
artificial radioactivity are many. The bombarded atom may disintegrate (e.g. disintegration of nitrogen atom when
struck by an α particle) and give radio-nuclides. Radio-actinium is formed by disintegration of actinium.
Bombarding boron with α particles gives radio-nitrogen. 198Au is produced by exposing a colloidal suspension of
metallic gold to neutrons. Alternatively, the bombarded nucleus may absorb the bombarding particle (as when a
hydrogen or nitrogen nucleus captures a slow (thermal) neutron). The transmuted nucleus then becomes radioactive.
Most of the radioactive materials in clinical use are artificial (226Radium is a notable exception), so that a material with the desired emission (preferably homogeneous and mono-energetic), and a suitable half-life may be used. In most cases 99mTc fits the bill. Half-life(T1/2 ): This is the time taken for a given radioactive material to lose half its radioactivity. Generally
speaking naturally radioactive substances have very long T1/2 (e.g. 235U and 40K have T1/2 of hundreds of years) and
artificial radioisotopes have T1/2 of hours/days, and occasionally months (tables 1a,b). Thus unnecessary radiation to
the body is minimised.
Units: The units commonly used to quantify the radiation burden in a sample of radioactive substance are Curie (Ci)
and Becqueral (Bq). Both are named after nuclear scientists. One micro-curie (μ Ci) and milli-curie (m Ci) are equal
to 10-6 and 10-3 Ci, respectively. [One m Ci = 37 MBq (Milli-Bq)].
Radio-nuclide imaging
Radio-nuclide imaging (RI) requires systemic administration of a radioisotope (tracer) following which it is; (a)
selectively concentrated in different parts of the body; and (b) differentially accumulated in diseased and normal
tissues in the same organ. It is simple to perform and relatively non-invasive. It is an innocuous approach to
evaluating organ structure and function and is suitable for initial screening examination of specific organ-systems.
Radioactive tracers reflect (but do not alter) organ function; assessment of physiological alterations represents the
most promising use of this diagnostic modality. However, demonstration of organ anatomy is better achieved by
USG, CT, spiral CT and MRI scans.
Safety considerations
Considering the potential harmful effects of ionising radiation on tissues as detailed in the previous issue, the
following points are noteworthy. (1) Emission: The isotope used in RI should emit, as far as possible, only γ rays.
These have low density of ionisation and low linear energy transfer (LET). (2) T1/2 : This should be few hours/days.
125I (T1/2 = 2 months), used to diagnose deep vein thrombosis, is a notable exception. RI mostly utilises artificial radioisotopes because they generally conform to these two criteria. Naturally occurring radioisotopes generally have long T1/2, and in any case their T1/2 and emission cannot be controlled. (3) Dose: This should be the minimum possible in order to reduce the radiation burden and not to alter organ function. The dose is determined, not by the pharmacological properties but by the radiation load. (4) Pharmacology: It should be rapidly excreted following completion of investigation, should not interfere with the physiology or biochemistry of the organ-system and should not have any undesirable effect on the organism as a whole. Most RI studies impose only about 0.1 to 0.5 rad of total body radiation, which is well within the safety limits. Radio-nuclides
Although well over 1000 radio-nuclides (RN) have been described, only a handful are in clinical use (tables 2a,b).
The therapeutic radioisotopes have been summarised in table 5 of the previous issue of this series.
Iodine (I)
Assessment of thyroid function with radio-iodine represents one of the first applications of isotopes in medicine.
Since the thyroid gland metabolises 131I in an identical manner to 127I (stable isotope), this is the one most frequently
used. Secondly, iodine has the maximum number of isotopes in clinical use, each with its own clinical significance
(table1b). Finally, radio-iodine can be attached as a radioactive label relatively easily to virtually any substance. This
makes it suitable for a wide variety of clinical uses. It is described more comprehensively in the next issue.
Technetium (99mTc)
It is a metallic element (AW = 99) and an artificial radioisotope (T1/2 = 6.03 hours). There are no stable isotopes or
natural radioisotopes. The 'm' in the superscript refers to a metastable state. It decays by isomeric transition, emitting
140 keV (kilo electron volts) γ rays. It is the most commonly used RN in nuclear medicine, with the most versatile
application and the maximum number of radio-pharmaceutical preparations to its credit. Its advantages are; (a)
convenient T1/2; (b) 140 keV photon emission is ideal for gamma camera performance (better image quality, shorter
imaging time); (c) pure γ emission makes it safe because of its low LET (see previous issue); and (d) absence of any
particulate emission, which if present, would markedly increase the radiation dose.
Radio-pharmaceuticals
Radio-pharmaceutical preparations (RP) containing 99mTc are the maximum in number compared to all other
radioisotopes and about 35 of them have been used clinically (tables 3a,b,c). The RP may be; (a) in ionic form
(99mTcO -
4 ) for brain imaging; (b) colloidal (sulphur) form for liver and spleen imaging; or (c) particulate form (albumin aggregated particles) for lung perfusion scanning. The 99mTc may exist in the form of ; (1) discrete
compound [sodium pertechnetate (Na99mTcO4)]; (2) radioactive label (99mTc-labelled RBC); (3) stannous (lead)
chelate (99mTc stannous pyrophosphate); (4) lipophilic neutral complex (99mTc teboroxime) ; or (5)lipophilic cation
complex (99mTc sestamibi).
99mTc pertechnetate: It binds loosely to plasma proteins and moves rapidly into the extra-vascular space after IV
injection. The pertechnetate (TcO -
4 ) anion attains a distribution similar to that of Cl- ions and concentrates in salivary glands, gastric mucosa, choroid plexus and thyroid gland. Cl- and I- are halides which share some common properties. This explains why 99mTcO - 4 is taken up by the thyroid in exactly the same way as 131I-,but the former is not organified in the gland like the latter. Therefore the 99mTc scan information may not be identical to 131I scan. Because of its wide distribution in body fluids and localisation in many organs, 99mTcO - RP in clinical practice. It is also used to prepare other radio-pharmaceuticals. In the normal brain the blood brain barrier (BBB) prevents entrance of 99mTcO - disruption of the BBB by any intra-cranial lesion, coupled with the vascularity of the lesion, allows high lesion-to-brain distribution ratio of the isotope; the lesion then appears as an area of increased uptake (positive scan). This contrast is possible because in normal areas of the brain where the BBB is intact, the uptake of 99mTcO - (negative scan).
99mTc sulphur colloid: Sulphur in colloidal form is labelled with 99mTc and injected IV. The reticuloendothelial cells
anywhere in the body (Kupffer cells in the liver, splenic red pulp, mononuclear-phagocytic cells in the marrow) treat
this preparation as foreign bodies and scavenge them, thus enabling visualisation of these organs.
99mTc-MAA:This is a sterile, aqueous suspension of macro-aggregated albumin (MAA) labelled with 99mTc,and is
used in lung perfusion scanning. This was found by Wagner et al in 1964 to give better results than perfusion
scanning with xenon gas dissolved in saline. MAA is produced by denaturing normal human serum albumin, to give
micro-spheres of controlled particle size (10-50μ, 10-75μ, 50-100μ etc). Following IV injection of the labelled
MAA, they are distributed in the lungs in proportion to their regional blood flow and remain trapped in the pre-
capillary arterioles/capillaries for a sufficient time for their γ emission to be detected. The size disparity between the
MAA particles and the pulmonary capillaries permit easy entrapment of the former, while their T1/2 of 6 hours (same
as 99mTc) allow sufficient time for gamma camera visualisation. Only about 0.1 % of the number of pulmonary
capillaries are occluded during the study, following which the particles fragment and disappear from the circulation,
thus making the procedure safe and free from adverse effects. This test can be performed even in severely dyspnoeic
patients.
99mTc-DTPA: Following IV injection of a sterile solution of labelled diethylenetriaminopenta acetic acid (DTPA), it
is concentrated through the functional renal tissue; non-functional areas such as cysts or tumours fail to concentrate
the isotope. This is the basis of renal scintiscanning and the information provided thus is similar to that obtained by a
nephrotomogram. [197Hg chlormerodrin or neohydrin may also be used for the same purpose].
A pair of gamma cameras placed over the renal areas can graphically record the individual renal functions in a
triphasic form (vascular, secretory and excretory phases) in the technique of radioisotope renography. [131I or 125I
may also be used for the same purpose].
Infusion of the same preparation may be used for renal function tests (viz. glomerular filtration rate, concentrating
ability, renal plasma flow etc). Unlike with creatinine, inulin or para-aminohippurate, the isotope technique does not
require total urine collection to evaluate the total renal function accurately. [Labelled chelate of EDTA may also be
used for the same purpose].
99mTc-etidronate, -MDP, -PYP: All are stannous chelates of 99mTc and the corresponding phosphorus-bearing
compound, and are used in bone imaging. Etidronate and MDP (methylene diphosphonate) are both diphosphonate
compounds that act as phosphate analogues and localise in bone. The former is not hydrolysed by enzymes, unlike
polyphosphates. PYP (pyrophosphate) is a linear polyphosphate that binds calcium and thus constitutes a highly
specific bone-seeking compound that accumulates in bone with kinetics similar to PO -
bone metabolism (inflammatory or neoplastic) results in increased tracer uptake. The PYP complex is also used in
acute myocardial infarction imaging because it is infarct-avid. The greatest affinity for the tracer occurs from 1 to 7
days after infarction and corresponds to the time of maximum Ca++ influx into the mitochondria of injured
myocardial cells.
99mTc-sestamibi, -teboroxime: Both are lipophilic complexes (cation complex of isonitrile and neutral complex of
boronic acid-quinolone, respectively) and are used in cardiac studies because of good myocardial uptake. The former
has minimum redistribution over several hours (suitable for cardiac imaging); the rapid myocardial clearance of the
latter makes it ideal for perfusion studies. 99mTc sestamibi has also been used to localise solitary parathyroid
adenoma.
99mTc-albumin: This is used in MUGA (multiple updated gated acquisition; gated blood pool) scan of the heart, to
record ventricular wall motion and ejection fraction (which constitutes ventricular performance). Following IV
injection the blood pool tracer equilibrates in the vasculature. Utilising a computer, multiple images are recorded
over a 10-minute period @ 20-30 frames per cardiac cycle, throughout many cardiac cycles. The term MUGA refers
to the fact that multiple 'gates' or time-windows at various times after the QRS complex are used to gather data.
99mTc-RBC: This is used in subtraction scintigraphy to improve the accuracy of a scan image, by producing image
enhancement. In the detection of gastrointestinal (GI) bleeding the labelled RBC are injected IV, from where they get
distributed in the body and are 'bled' out from the site of GI bleeding. The site is detected as an area of increased
radioactivity. But in very minute / slow bleeding, this may be masked by the general background radioactivity. If 5-
minute interval images are taken and each is digitally subtracted from the one immediately after it, the background
radioactivity can largely be eliminated, allowing the bleeding site to be highlighted. This is the principle of
sequential subtraction scintigraphy. It can detect bleeding rates as low as 0.05 ml min-1 and the minimum detectable
activity volume is 0.5 ml at 10 minutes (as opposed to 3 ml by conventional non-subtraction scintigraphy)1.
Subtraction is also used to enhance a tumour image in the technique of radioimmunolocalization of tumours
(immunoscintigraphy). When 131I-labelled monoclonal antibody (MAB) is injected IV, it localises on the tumour and
also on the thyroid, liver, spleen and urinary bladder. The blood pool is separately labelled with 99mTc-RBC and the
general blood pool image is digitally subtracted from the 131I-MAB image. This enhances the tumour image2.
99mTc-PG, -IDA: The N-substitution of the imino group in iminodiacetic acid (IDA) gives various derivatives; viz.
DISIDA, PIPIDA, DIDA (diethyl IDA), HIDA (dimethyl acetanilide IDA). These or pyridoxilidine glutamate (PG)
are labelled with 99mTc to give the corresponding radio-pharmaceutical. After IV injection they are promptly taken up
by the hepatocytes, excreted into the bile and thence into the gallbladder and intestine. Normally the entire biliary
tree is visualised and the presence of activity in the intestine indicates a patent biliary tract. Visualisation of the cystic
duct and gallbladder rules out acute cholecystitis. Interest in cholescintigraphy has been revived by the development
of these agents to replace the age-old 131I-Rose Bengal and the technique has been refined by computer data analysis
and liver subtraction (see under 'Cholescintiscan' for more details).
Imaging techniques
The γ rays emitted by 99mTc are detected by a scintillation counter (activated sodium iodide (NaI) crystal). When γ
rays strike this crystal, light is produced. When this light hits the photo-cathode of a photo-multiplier tube electrons
are released which are amplified to give an electrical pulse. This pulse is further amplified and analysed by an
electrical processing unit and a recording is then made. The radiation from the isotope taken up by organs in the
body can be recorded by the following methods.
Rectilinear scanner: In this machine the crystal detector mechanism is moved backwards and forwards in a grid-
like pattern over the area being scanned. The result is usually recorded photographically as a printout of dots which
vary in number with the intensity of radiation at different sites.
Anger gamma camera: The detecting surface of this instrument consists of a large NaI scintillation crystal, 25 to 50
cm in diameter, coupled to an array of photo-multiplier tubes arranged as a circular detector with a large field of
view, which electronically positions the gamma interactions detected by the crystal. The large field of view afforded
by the array of tubes allows large areas (viz. both lungs or liver and spleen) to be examined without having to move
either the patient or the detector. The gamma camera is much more sensitive than the rectilinear scanner and takes
much less time to build up a picture. Therefore it is most commonly used to image the distribution of radioactivity.
Imaging: The data from the gamma camera may be digitised for computer processing or viewed as an analogue
image. This may be seen on a cathode ray tube (CRT) or on a television screen or stored on videotape, radiographic
film or special photographic film. On a CRT and a developed photographic film, areas of increased photon emission
appear as areas of increased brightness and blackness, respectively.
Emission vs. camera function: The gamma camera functions optimally at particular levels of energy emission. The
140 keV of photon emission of 99mTc is ideal for detection by the standard gamma cameras. The high energy of
emission by 131I (γ and β) is associated with a relatively low efficiency of detection by the gamma camera. This limits
the resolution of the image and may give false-negative results. The relatively low energy of γ emission by 123I is
more efficiently detected by the gamma camera. The γ emission of 111Indium (In) is also in the suitable range.2
Tomoscintigraphy
This is also known as emission tomography and gives an opportunity to visualise the distribution of the isotope and
obtain a 3-dimensional image. 111Indium is more suitable for this than 131I. Comparison of tomoscintigraphy with
conventional rectilinear immunoscintigraphy has shown that the former detects smaller tumour sites (10 cm3 vs. 50
cm3) and has a higher detection rate (94% vs. 43%)2. Positron emission tomography (PET) uses short-lived, on-the-
spot cyclotron-produced positron-emitting radio-nuclides to obtain axial images of the brain, depicting its functional
status.
Cholescintiscan
Though 131I-Rose Bengal has been in use traditionally, 99mTc-HIDA, -DIDA, -PIPIDA, -DISIDA, -PG are better.
They are all excreted by the hepatocytes into the bile and thence into the intestine.
Obstructive conditions
Visualisation of radioactivity in the intestine (or otherwise) is used as the criterion to diagnose; (a) congenital biliary
atresia; (b) biliary-enteric anastomotic patency; and (c) complete biliary obstruction in jaundiced patients. In the last
situation, since the isotope is not excreted through the biliary system but through the kidneys, the scan image is less
satisfactory than PTC, ERCP or USG in diagnosing the obstructive condition. Definition of isotope scanned image is
not as good as conventional radiology. However, its role in acute cholecystitis appears promising.
Acute cholecystitis
Evidence of patent cystic duct and visualisation of the gallbladder excludes the diagnosis of acute cholecystitis (AC)
in the vast majority of patients. Conversely, non-visualisation of the cystic duct and gallbladder (due to obstruction
of the cystic duct) but visualisation of the CBD is diagnostic of AC in a high percentage of patients.
Delayed imaging: Since certain conditions may affect gallbladder contraction, delayed imaging may highlight the
same along with the cystic duct in many cases which were negative in the early films. However some recent studies
suggest that non-visualisation even on delayed images of cholescintigraphy is a non-specific finding (i.e. it does not
confirm AC).
Sincalide pre-treatment: Cholecystokinin (CCK; sincalide: stimulant of gallbladder contraction ) is administered IV
over 3-5 minutes @ 0.02 μg kg-1, followed by 185-481 MBq (5-13 m Ci) of 99mTc-mebrofenin (adjusted to patients'
bilirubin levels), and sequential imaging is performed until gallbladder activity is identified or till 90 minutes post-
injection of 99mTc. Sincalide pre-treatment, when administered at the physiological rate, is helpful when functional
resistance to tracer flow into the gallbladder is present. CCK pre-treatment does not obviate the need for delayed
imaging when the morphine augmentation technique (infra) is not used.
Morphine augmentation: Morphine produces spasm of sphincter of Oddi and improves visualisation, with or
without sincalide pre-treatment. It has a reasonably good, though imperfect, specificity and positive predictive value,
which are significantly better than for delayed imaging, apart from its logistical advantage (shorter imaging time).
This technique is therefore recommended for routine clinical use in patients with non-visualisation of the gallbladder
at 1 hour. After sincalide pre-treatment if there is no visualisation till 90 minutes, a second dose of tracer is injected,
followed by morphine sulphate (@ 0.04 mg kg-1) and imaging is done for 30 minutes or till gallbladder visualisation.
This significantly increases the frequency of gallbladder visualisation (from 72% to 84%, in one study) and improves
the efficacy of the test3,4.
Tracer vs. IVC: The findings described above (excluding or confirming AC) are similar to intravenous
cholangiography (IVC), but the accuracy is more with isotope scanning, there is no risk of hypersensitivity reactions
(as with IVC) and it can be done on patients with serum bilirubin levels as high as 8 mg % (as against 4 mg % with
IVC). Radioisotope scanning is rapid, simple and safe for diagnosing AC in emergency admissions.
Parathyroid scan
Accurate pre-operative localisation of the parathyroid gland is difficult because of many reasons (table 4). A solitary
adenoma is the most common finding (multiple in 6% of cases only). For the surgeon, inability to identify such an
adenoma in a normal anatomical location constitutes his Waterloo, and that is the primary reason of failure at the
initial neck exploration. Table 4 lists a few localisation techniques.
Radio-immunoassay (RIA): This was developed by Berson and Yallow in 1963. The several immunologically and
biologically distinct species of parathormone (PTH) in plasma necessitate a non-homologous assay system (labelled
bovine PTH and bovine PTH antiserum) to measure human PTH in blood. RIA is applied to selective venous samples
(obtained by percutaneous catheterisation) from veins of the neck and thorax, in order to localise the parathyroid pre-
operatively. But selective venous sampling allows only lateralisation (not localisation) of single adenoma (denoted
by marked unilateral gradient in PTH concentration in small thyroid veins), and is also unhelpful in 4-gland
hyperplasia (denoted by gradients in PTH concentration on both sides of thyroid plexus). Thus, selective thyroid
arteriography, guided by venous sampling results, is often more helpful in localisation. These invasive methods are
used for cases with persistent / recurrent hyperparathyroidism following neck operation.
75Se-methionine scan: The labelled amino acid is taken up by the gland for PTH production. Scanning is; (a) non-
invasive; (b) often helpful in identifying large parathyroid neoplasms; and (c) rarely helpful in localising the more
common smaller ones. The same points apply to thermography (recording the infrared rays emitted by the gland).
99mTc sestamibi scan: This has been recently introduced for parathyroid localisation5. It has; (a) a success rate of
85% in pre-operative adenoma localisation; (b) improves the success rate of resection at first neck exploration; (c)
gives 27% reduction in bilateral neck exploration time ; and (d) is a likely predictor of multigland disease also. The
scan uses a double-phase, delayed imaging technique. The adenoma concentrates the isotope and appears as a focal
spot of delayed tracer washout in the late image (positive scan). Thyroid nodules also show the same characteristics,
thus accounting for 15% of false-positive scan with respect to parathyroid adenoma. Absence of focal delayed
washout of tracer constitutes a 'negative scan' for solitary adenoma, but is a highly accurate (nearly 100%) pre-
operative predictor of multigland disease. Thus a 'negative scan' allows for preparation for cryopreservation for
subsequent autotransplantation5.
Adrenal scan
Beierwaltes et al introduced the technique in 1971. Normal adrenal glands are easily identified by their uptake of 131I-
labelled cholesterol, a precursor in the synthesis of corticosteroids.
Preparations: 19-(131I)iodocholesterol and 6B-(131I)iodomethyl-19-norcholesterol are taken up by the adrenal cortex
in the usual way following injection. A major disadvantage with the former preparation is the necessity to perform
repeat scans 4 to 19 days later to identify the cortical pathology. This is obviated by the latter preparation.
Cortical pathology: Adrenocortical tumours may be visualised by these techniques. The second preparation has been
used in primary aldosteronism (Conn's syndrome) where there is excessive mineralocorticoid (aldosterone)
production due to adrenocortical adenoma, hyperplasia or carcinoma. However, carcinomas frequently fail to be
visualised because they do not concentrate the tracer efficiently, unlike the normal cortex.
Medullary tumours: Adrenal medulla is the largest paraganglion (collection of neural crest cells adjacent to the
ganglia of the autonomic nervous system). All functional (i.e. catecholamine-secreting) paragangliomas, whether
chromaffin or non-chromaffin (i.e. staining positive or negative with chromic salts), are nowadays termed
pheochromocytoma. These may be in the adrenal medulla or extra-adrenal. Locating the latter presents a formidable
problem because they may be situated anywhere from the thorax to pelvis (wherever there are cells of the
sympathetic nervous system or other chromaffin cells whose embryological origin is in common with that of the
autonomic nervous system). Even adrenal pheochromocytomas are very difficult to discern by isotope scanning
techniques because; (a) the tracers are not concentrated by the adrenal medulla because their secretions do not utilise
cholesterol as a precursor; and (b) the medullary tumours may markedly displace or attenuate the surrounding cortex.
However, large tumours may occasionally be demonstrated by adrenal scans.
Adrenal scans in general are of extremely limited value in detecting adrenal lesions. CT scan (resolution < 2 cm;
smallest lesion identified so far has been 1 cm) is the preferred choice in this regard.
Renal scan: There may be downward displacement or extrinsic compression of the kidney by a large adrenal mass.
Less than 50% of adrenal lesions are detected by this technique. Valuable ancillary information and functional
integrity of the kidneys can be documented by renal scans (infra).
'Incidentaloma': This is an adrenal mass (clinically asymptomatic) incidentally discovered by imaging. The
incidence of discovery of incidentalomas has increased with the advent and application of sensitive non-invasive
imaging techniques. When an incidentaloma has been discovered, adrenal (cortical and medullary) functions should
be tested and it should be removed if it is; (a) hormonally active; (b) suspected to be malignant; and (c) > 6 cm.
Others should be followed by CT scan at 3, 9 and 18 months after the initial diagnosis 6.
Pancreatic scan
Apudomas
These are tumours arising from the apud (Amine Precursor Uptake Decarboxylation)cells, which are argyrophilic
(have affinity for silver salts) and are distributed throughout a diffuse neuroendocrine system (predominantly in the
gut mucosa, medullary (C) cells of the thyroid and pancreatic islets of Langerhan). Based their secretion they are
termed; (a) gastrinoma; (b) insulinoma; (c) glucagonoma; (d) somatostatinoma; (e) pancreatic peptidoma (PPoma);
(f) VIPoma; and (g) residioblastoma.
Isotope scan: Most techniques have attempted to localise pancreatic apudomas, with variable success. The small size
and multiplicity of these tumours make detection difficult or impossible.
RIA-(peptides): The principle is the same as for parathyroid adenoma localisation. Trans-hepatic selective portal
venous catheterisation and RIA of the venous sample may show a sudden step-up in the peptide hormone
concentration. By combining this with selective pancreatic arteriography and employing a subtraction technique a
high proportion of apudomas can be identified. Predominant secretion by hepatic metastases may also be detected by
simultaneous hepatic vein sampling 7.
RIA-(NSE): Neuron-specific enolase (NSE), a neural form of the glycolytic enzyme, enolase, is produced in large
quantities by all types of apudomas (but not by non-endocrine tumours), and its elevated levels in the plasma of such
patients can be detected by RIA. NSE is thus a tumour marker. NSE assay may be important in the diagnosis of
apudomas and for monitoring the response to therapy7.
Immunoscintigraphy: 131I-anti-insulin antibody in polyclonal antiserum has been used to radioimmunolocalise
pancreatic insulinoma2 (see under 'Radioimmunolocalisation' in the next issue).
75Se-methionine: This is only of historical interest today. Radio-labelling methionine by replacing its sulphur with
75Selenium does not change its metabolic properties. It is taken up by the pancreas and concentrated sufficiently to be
imaged by gamma camera. However, simultaneous liver uptake often obscures the pancreatic image. Because of this
and the better definition obtained by other modalities of imaging the pancreas, 75Se-methionine scan is no longer
used for the pancreas.
Renal scan
Renal function tests: Evaluation of the total renal function (glomerular filtration rate, renal plasma flow etc) is
achieved by measuring the degree of retention in the blood, and excretion of, IV infused radioactive substances (table
5). These do not require total urine collection, unlike urea, creatinine (endogenous substances) or inulin, para-
aminohippurate, PSP (exogenous substances), which depend on total urine collection, and give inaccurate results
when there is significant residual urine.
Radioisotope renogram: This indicates the individual renal function in a qualitative fashion. Following IV injection
of a radioisotope, gamma cameras over each renal area measure the; (a) rate of renal blood flow and uptake; the
vascular spike (an initial steep rise of ½ minute); (b) rate of renal concentration, by accumulation of radioactivity,
dependent on renal function (4-6 minutes); and (c) rate of clearance of the substance, by a decrease in radioactivity to
blood levels, dependent on excretion. This is the triphasic graphic representation of the normal kidneys. Abnormal
findings are given in table 6. If urine, blood and an inactive of the body are simultaneously monitored, additional
information can be obtained. The 'blood graph' matches all the 3 phases of the renogram except that all the phases
occur faster and the peak is higher. A simultaneously obtained dynamic renal scintiscan (infra) adds anatomical
information, and computerised analysis permits quantitative interpretation of individual renal function.
Scintiscan: The isotopes (table 5) are concentrated throughout the functioning renal tissue and provide excellent
definition and functional assessment. Areas of non-functioning tissue (cysts, tumours, abscesses etc) do not
concentrate the isotope, and show as filling defects in the static scan.

The subsequent issues will contain scanning techniques of all the other organ-systems of the body.

References
1. Wu Y, Seto H et al. Sequential subtraction scintigraphy with 99Tcm-RBC for the early detection of gastrointestinal bleeding and the calculation of bleeding rates: Phantom and animal studies. Nucl Med Commun, 1997, 18(2): 129-138. 2. Hardcastle JD, Baldwin RW. Monoclonal antibodies. In: Russell RCG (Ed.). Recent Advances in Surgery, Vol. 12. London, Churchill Livingstone, 1986: 43-56. 3. Chen CC, Holder LE et al. Morphine augmentation increases gallbladder visualisation in patients pretreated with cholecystokinin. J Nucl Med, 1997, 38(4): 644-647. 4. Kim CK. Pharmacologic intervention for the diagnosis of acute cholecystitis: Cholecystokinin pretreatment or morphine or both. J Nucl Med, 1997, 38(4): 647)649. 5. Carter WB, Sarfati MR et al. Preoperative detection of sporadic parathyroid adenomas using technetium-99m sestamibi: What role in clinical practice? Am Surg, 1997, 63(4): 317-321. 6. Bastounis EA, Karayiannakis AJ et al. Incidentalomas of the adrenal gland: Diagnostic and therapeutic implications. Am Surg, 1997, 63(4): 356-360. 7. Sagor GR, Baron JH et al. The clinical relevance of regulatory peptides. In: Russell RCG (Ed.). Recent Advances in Surgery, Vol 11. London, Churchill Livingstone, 1982: 1-25. Table-1A
Radioisotopes: Half-lives and characteristics
Element Isotope(s) Half-life
Comments
195, 198, 199 2.5 days (198 Procured fresh from atomic pile for bladder cancer therapy (198 Au) , used Au for scintiscan and cancer therapy (all isotopes) Study of potassium interchange in the body Study of blood flow, water balance, peripheral vascular disease, renal function tests (see text) Importance in clinical scintiscan and nuclear fallout lies in Needs chelating agent to form radio-ligand Can be stored in hospital for bladder cancer therapy Cancer therapy; produces α particles and 222 Radon Ra A, B, C are decay products of 222 Radon Ra B, C give β and γ radiation and are used in clinical therapy Acronym for radium emanation; gas and solid form; emits α particles; seeds used in cancer therapy Table-1B
Radioisotopes and half lives
Elements Isotope(s)
Half-life
Table-2A
Light radio-nuclides (AW < 80) and their diagnostic applications
Radioisotopes Salt/preparation/radio-pharmaceutical/
Uses / applications
radioligand
3 H {Tritium; heavy hydrogen, Tritium incorporated in thymidine of DNA Cellular proliferation, turnover and (1 proton, 2 neutrons)}; stable (tritiated thymidine-labelled cells) H has 1proton and no neutrons 13, 14 Carbon Radiocarbon urea {CO(NH2)2}, giving Urea breath test for gastric H. pylori; radiocarbon dioxide (CO2) Bone scan for breast cancer metastases (few studies; see text) 32 Phosphorus(P); (AN=15, Diisopropylfluoro(32P)phosphate; colloidal RBC life span, splenic scan, AW=30.974) polycythaemia vera treatment; liver blood flow studies Sodium(51Cr)chromate (Na2CrO4)-tagged RBC, platelet life span; splenic scan RBC 57, 58 Cobalt (Co); (AN=27, (Radio-cobalt) cyanocobalamin (vitamin Schilling test, renal function tests, AW=58.9332) Soft tissue inflammation and cancer scan (liver, lung, mediastinal nodes, seminoma metastases, Hodgkin's, malignant lymphoma) Selenomethionine (sulphur in methionine Thyroid, pancreas scan (obsolete) substituted with 75Se)
Table-2B
Heavy radio-nuclides (AW > 80) and their diagnostic applications
Radioisotopes
Salt / preparation
Uses / clinical applications
99 Molybdenum (Mo) Ammonium(99Mo)molybdate Liver 111In-labelled monoclonal antibodies Tomo-/immunoscintigraphy (tumour (MAB) 127,133Xe gas (inhalation), dissolved in Lung ventilation scan, thermal inhalation injury saline (IV injection) scan, ventilation-perfusion scintiphotography, brain perfusion scan Radioisotope renogram, renal scintiscan, brain scan Cardiac scan for ischaemia (after stress and dipyridamole) *Radioactive arsenic (brain scan) and radioactive bromine (bone metastases scan) have also been used. Radioactive thorium (thorotrast) was
once used for cerebral ventriculography and arteriography. However it remains trapped in the splenic red pulp till 20 years and produces
radiation fibrosis and hyposplenism. Hence its use has been discontinued.


Table-3A
Clinical applications of 99mTc radio-pharmaceuticals

99mTc radio-pharmaceuticals
Clinical applications
1 99mTc pertechnetate; ionic pertechnetate (TcO - 4 ) as Scan of brain, thyroid, salivary gland, stomach, heart, joints, Meckel's diverticulum; preparation of other 99mTc radio-pharmaceuticals 2 99mTc sulphur colloid; a.k.a. colloidal technetium sulphide Liver blood flow studies, liver and spleen scan 3 99mTc-MAA; (macro-aggregated albumin); a.k.a. Lung perfusion scan, venous thrombosis scan 4 99mTc-DTPA; (diethylenetriaminopenta acetic acid); a.k.a. Kidney, brain, lung scan; renal function tests, 99mTc pentetate (99mTc complexed with pentetic acid in radioisotope renogram NaCl solution) 5 99mTc MDP; (methylene diphosphonate); stannous chelate Skeletal imaging (diphosphonate localises in bone) 6 99mTc etidronate; stannous chelate of 99mTc and etidronate, Bone scan (this diphosphonate not hydrolysed by
Table-3B
99mTc radio-pharmaceuticals (continued)
99mTc radio-pharmaceuticals
Clinical applications
99mTc-PYP; (pyrophosphate); complex of tin (stannous) Skeletal imaging (affinity for Ca++, distribution like and PYP labelled with 99mTc 4 ); MI scintigraphy (affinity for Ca++); 99mTc sestamibi; (hexakis 2-methoxyisobutyl nitrile); Cardiac imaging (good myocardial uptake, minimal lipophilic monovalent cation complex of isocyanide redistribution over several hours); solitary parathyroid (isonitrile) family containing 99mTc 99mTc teboroxime; lipophilic neutral complex of boronic Myocardial perfusion studies (good myocardial uptake acid, 99mTc and 8-hydroxyquinoline (BATO) 10 99mTc albumin; normal human serum albumin labelled Dynamic radio-nuclide angiocardiography (MUGA 11 99mTc-RBC; red blood cells labelled with 99mTc Sequential subtraction scintigraphy for GI bleeding; contrast enhancement in tumour immunoscintigraphy 12 99mTc-IDA; (iminodiacetic acid); HIDA(dimethyl Cholescintigraphy (acute cholecystitis, atresia, biliary- acetanilide IDA), DIDA(diethyl IDA), DISIDA and enteric anastomotic patency, biliary obstruction) PIPIDA labelled with 99mTc 13 99mTc-PG; (pyridoxilidine glutamate) Note: (A) Soft tissue organ scan (#1to 4); (B) bone scan (#5 to 7); (C) cardiac scan (# 7 to 10); (D) contrast enhancement (# 11);
(E) biliary scan (# 12 and 13)
Table-3C
99mTc radio-pharmaceuticals which are of limited use
99mTc albumin colloid
99mTc dicarboxypropane-diphosphate 99mTc hexamethyl propylenamineoxime 99mTc N-piperidinyl ethyl- *See text under "Cholescintigraphy". Methods of parathyroid localisation
Non-invasive (pre-operative)
Invasive (after failed operation)
Isotopic Non
-isotopic
Causes of difficulty in localisation
1. Small (0.5-1cm) even when hyperplastic 2.Variable position: From pharyngeal mucosa (upper extreme limit, rare) to thymus in upper anterior mediastinum {lower extreme limit, more common (5%)} 3. Variable number: 2-7 (Alveryd's series - 1968) 4. May be intra-thyroidal: Superior parathyroids and lateral thyroid complex are from 4th pharyngeal pouch 5. May be intra-thymic: Inferior parathyroids and thymus are from 3rd pharyngeal pouch Dual problem: difficult pre-operative localisation; difficult intra-operative identification Isotopes used for renal studies
57Co-, 58Co-cyanocobalamin (vitamin B12) 99mTc-EDTA (ethylenediaminotetra acetic acid) 99mTc-DTPA (diethylenetriaminopenta acetic acid)99m 23Na-iodohippurate (Hippuran) 125I-, 131I-diatrizoate (Hypaque) 197 Radioisotope renogram findings
Slow first phase Low peak Shallow (slow) third phase, plateau midway between peak and base Slow first phase No third phase, high plateau Renal artery stenosis First phase even slower Very low peak Quick fall to basal levels

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