Page 29 - ARNM-2-3

Advances in Radiotherapy
& Nuclear Medicine QC parameters in radiopharmaceuticals

particularly crucial. Short-lived radiopharmaceuticals, Tachypleus tridentatus, and Carcinoscorpius rotundicauda.
including those labeled with the radionuclides Ga or F The basic test principle is based on the idea that endotoxin
68
18
(t = 68 or 110 min, respectively), are frequently only tested will generate an opaque gel in the presence of Ca ion
2+
1/2
for sterility after the radioactivity has decayed, which might when the sample is incubated with the LAL at 37 ± 1°C.
produce false results. Long-lived radiopharmaceuticals A test sample with a pH range of 6 – 8 and 0.1 mL LAL
having half-lives of days to weeks (such as Lu, I, or Y) typically makes up an assay mixture. After mixing, the
131
90
177
require several days to months to decay, which can alter reaction takes place for 60 ± 2 min. The development of
the outcome of the sterility test because of their prolonged an opaque gel shows the existence of an endotoxin. The
incubation time. The microorganisms often die after a LAL test is performed on LAL reagent water, control
particular time frame due to the lack of nutrients or other standard endotoxin from Escherichia coli, and test samples.
factors and are not detected in the later stage of sterility Depending on whether test materials form gel, they are
testing. In this regard, alternative microbiological methods classified as either positive or negative with respect to the
30
mentioned in pharmacopeias have proven the potential for control standard endotoxin from E. coli, which acts as a
results in real-time or almost real-time with the prospect positive control if gel formation takes place, and the LAL
of earlier corrective action. If these novel approaches are reagent water acts as a negative control in the case of no gel
proven effective and made suitable for regular usage, the formation. 35-38 The endotoxin limit required for a bacterial
quality of testing may likewise be significantly enhanced. endotoxin test is mentioned in the individual monograph
Several in vitro sterility tests used rapid testing techniques of the pharmacopeias, whereas a comparative status of
to determine the presence or absence of microorganisms endotoxin limit calculation of different pharmacopeias
by measuring the evolution of CO or consumption of O based on radiopharmaceutical product administration is
2
2
for detecting bacterial metabolism in closed containers, mentioned in Table 3. 9-15 For radiopharmaceuticals created
thus helping to overcome this significant limitation. The using short-lived radioisotopes, endotoxin testing after
basic principle of the test involves the addition of the product release is permissible. However, developing the
test sample to a trypticase soy broth culture medium kinetic (photometric) LAL test, which may be accomplished
that contains C-glucose. The capture of CO gas in in 20 min, has made it possible to test for bacterial
14
14
2
this method shows the existence of both aerobic and endotoxin before releasing the radiopharmaceuticals with
anaerobic microorganisms. A rapid testing approach also half-lives longer than 30 min. 9-15
uses ATP bioluminescence to get beyond the drawbacks
of conventional test methods for radiopharmaceutical 6.2.2. Risks of radiopharmaceutical endotoxin
quality control, improving data integrity and subjectivity contamination
removal. 31-33 The innovative aspect of this approach is that Like all other drugs, radiopharmaceuticals are governed
it only requires a short testing duration, roughly 3 – 24 h by stringent endotoxin contamination restrictions. Due
instead of several days. to potential interference with the assay’s components,
6.2. Apyrogenicity caution must be used when performing the LAL assay
on radiopharmaceuticals. The availability of free Ca
2+
6.2.1. Bacterial endotoxin test ions is essential for the key enzyme transglutaminase in
A test for bacterial endotoxin is recommended for several the LAL assay. Chelating compounds, which reduce the
2+
radiopharmaceutical formulations. The test is conducted amount of Ca in the solution, are typically found in
following the general method of bacterial endotoxin, radiopharmaceuticals. As a result, the LAL assay could
adopting the appropriate safety steps to limit radiation produce erroneous negative results. A 2014 study published
exposure to the personnel carrying out the test. Bacterial in the Journal of Nuclear Medical Technology offered a
9
endotoxin is the only necessary pyrogen of concern in simple but efficient approach to eliminating this issue.
parenteral drug preparations because of its potency and The scientists added more calcium chloride to prepare
widespread natural distribution. Depending on the dose, the drug for LAL testing. By doing this, they successfully
mode, and rate of administration, bacterial endotoxins eliminated interference from the chelating chemicals in the
might have adverse effects. Limulus amebocyte lysate radiopharmaceutical. 39
(LAL) reagent is economically feasible for routine bacterial
endotoxin tests based on gel-clot formation. The LAL 6.2.3. Rabbit pyrogen test
34
test, commonly known as the bacterial endotoxin test, is The test for rabbit pyrogen may be particularly
used to detect endotoxin quantitatively and qualitatively. emphasized for testing the product when the nature
This method uses the amebocyte lysate from the horseshoe of the radiopharmaceutical preparation results in
crab’s blood, such as Limulus polyphemus, Tachypleus gigas, interference through inhibition or activation, and it is

Volume 2 Issue 3 (2024) 9 doi: 10.36922/arnm.3619