Radiopharmaceuticals
in over 80 000 administered doses in this study [3].
See also Thorotrast
GENERAL INFORMATION
Radioactive substances may be used in medicine as tracers,
the quantities used in this case being merely sufficient to
enable them to be detected, or as therapeutic agents, in
which case the quantities employed and the amount of radi-
ation emitted may be considerable. Risks resulting from the
radiation itself fall outside the scope of this volume.
Radio-iodine is covered in a separate monograph.
General adverse effects and adverse
reactions
Radiopharmaceuticals have a good safety record. The
prevalence of adverse reactions is approximately 1000-
fold than less than that occurring with iodinated contrast
media and drugs. The Society of Nuclear Medicine has
maintained a register of adverse reactions to radiophar-
maceuticals occurring in USA since 1976. The frequency
of reactions appears to be falling because of improved
quality control of radiopharmaceuticals. Many of the ear-
lier adverse reactions were attributed to iron-containing
formulations, gelatin-stabilized formulations, materials
such as albumin contaminated with pyrogens, and other
products no longer in use. The overall incidence of reac-
tions for the year 1978 was estimated to be 1–6 per 100 000
examinations [1].
In order to determine the prevalence of adverse reac-
tions to radiopharmaceuticals, a 5-year prospective study
(1989–94) was performed in 18 institutions in the USA [2].
The reported incidence rate was 0.0023%. No adverse
reaction required hospitalization or had significant
sequelae. The adverse reactions and types of radiophar-
maceuticals are shown in Table 1.
Another study was undertaken to determine the preva-
lence of adverse reactions to positron-emitting radiophar-
maceuticals through a prospective 4-year study in 22
institutions. PET radiopharmaceuticals have an excellent
Table 1 Adverse reactions to 783 525 radiopharmaceutical doses in 1989–94 in the USA (n ¼ 18)
Radiopharmaceutical
67
Gallium citrate
[131I] Iobenguane (MIBG)
99m
Tc-macroaggregated albumin
99m
Tc-medronate (MDP)
99m
Tc-oxidronate (HDP)
99m
Tc-pentetate (DTPA)
99m
Tc-sestamibi
99m
Tc-sulfur colloid
Stannous pyrophosphate (non-radioactive)*
*Given intravenously to allow in vivo radiolabeling of erythrocytes and considered part of the final radiopharmaceutical.
ã 2016 Elsevier B.V. All rights reserved.
safety record because no adverse reactions were reported
In a review of UK reports of adverse reactions to radio-
pharmaceuticals from 1977 to 1983, there was a changing
distribution pattern with time (Table 2) [4]. This was
partly due to elimination of some of the earlier, more
toxic formulations and partly due to changing usage,
more particularly the increased use of phosphonate for-
mulations. The authors estimated that only 10% of reac-
tions were reported and that the probable incidence rate
was between one in 1000 and one in 10 000. There was one
death associated with a hypotensive reaction to colloid in
a severely ill patient. One elderly patient had a cardiac
arrest after injection of macro-aggregated albumin but
was resuscitated. In a European prospective survey during
1996, there was a prevalence of 11 events per 105 admin-
istrations of radio-pharmaceuticals. No serious or life-
threatening events were reported [5].
99m
Technetium
The widespread use of 99mTc-diethylaminetriaminepenta-
acetate (DTPA), mostly used for renal imaging, has
brought with it a number of reported DTPA adverse
reactions. Typical symptoms include low pressure, loss of
consciousness, feeling faint and occasionally rashes and
bronchospasm. In Europe, a patient with a history of
asthma developed severe bronchospasm and died within
a matter of minutes [6]. A series of very serious problem
developed following intrathecal injection of 99mTc-DTPA
in what turned out to be, strictly speaking, a misformula-
tion incident. Almost all currently used DTPA formula-
tions contain the mixed calcium/sodium salt of DTPA.
However, one particular manufacturer used the trisodium
salt. This form is capable of chelation of cerebrospinal
fluid calcium and magnesium and causing gradual onset
of severe neurological signs and severe paresthesia [7].
99m
Tc-labeled serum albumin microspheres have in one
case caused collapse, apparently because the patient
in question had earlier been sensitized by blood transfu-
sions [8].
A case of anaphylaxis occurred after the injection of a
leukocyte suspension labeled with 99mTc-hexamethyl pro-
pylene amine oxime [9].
Adverse reaction Number
Rash 1
Chest discomfort, light-headedness 1
Rash 1
Rash/nausea/mild anaphylaxis 2/1/1
Rash/sweating 4/1
Rash 1
Rash 1
Nausea, vomiting, rash, headache 1
Mild anaphylaxis/light-headedness 2/1