ATOM INDONESIA
Referee’s Report
Article No.: # 741
Title of Paper: Pharmacokinetics Interaction of Non-Steroid Anti Inflammatory Drugs to 99mTc- MDPRadiopharmaceuticals for Bone Imaging and Its Biodistribution
Suggested change to:
Pharmacokinetics Interaction of Non-Steroid Anti Inflammatory Drugs with 99mTc-MDP Radiopharmaceuticals for Bone Imaging
Line # Referee’s Comments
12 -13
….drugs, meloxicam and natrium diclofenac with….….
….by injecting 100 mCi/ 100 mL 99mTc-MDP intravenously.
Blood samples were withdrawn from each mouse which were then weighted and counted using single channel analyzer.
The pharmacokinetic profile (%ID/g??) of 99mTc-MDP in blood of normal/ untreated (Group I), treated with meloxicam (Group II) and natrium diclofenac (Group III) mice 5 minutes post injection were 3.71, 8.96 and 9.15% respectively, then decrease to 0.12, 0.01, and 0.01% respectively 24 hours post injection.
…T-test showed there was no….in distribution 99mTc-MDP of in normal/ untreated mice (Group I) and in treated mice either with meloxicam (Group II) or natrium diclofenac (Group III). However, there was significant difference in elimination of 99mTc-MDP in normal/ untreated mice (Group I) and in treated mice either with meloxicam (Group II) or natrium diclofenac (Group III).
Results of biodistribution study…please refer to correction 213-230. This part of abstract up to line 13 needs to be rewritten.
16-25 It’s suggested to be removed. It’s unnecessary statement.
33 …compounds such as…
71 Remove The. Materials used…
74 …HCl dan acetone (E. Merck), NaCl 0.9%, aquabidest (IPHA) 76 …3MM Whatman chromatography paper
78. …(Merck). In-house prepared MDP radiopharmaceuticals kits.
84-90 These lines should be deleted. There are duplications (see previous lines)!!!
93 All steps 93-96
Please do not use number as a subject of a sentence!!!
99mTc-Pertecnetate (3 mL, 3 mC) was added into vial containing MDP kit.
96 The solution was shook…..at room temperature resulted in 99mTc-MDP radiopharmaceutical.
99
Radiochemical purity of 99mTc-MDP was determined using 2 paper chromatography systems. The first one is using 3MM Whatman chromatography paper as stationary phase and 100% acetone for separating reduced- 99mTc (99mTcO2) and 99mTc-MDP from 99mTc- Pertecnetate. The second one is using 3MM Whatman chromatography paper as stationary phase and 0.9% NaCl as a mobile phase for separating 99mTcO2 from 99mTc-MDP and 99mTc- Pertecnetate [Ref].
108-
109 This research….. This sentence is suggested to be removed. It’s unnecessary statement 115 …except in…
125 …test used…
128 and III. The treated mice were injected with ….injected through their tail veins 130 At specified time….
132- 134
...99mTc-MDP, blood samples were withdrawn from the tail of each mouse. Blood samples were then weighted and counted using …single channel analyzer Na(I)Tl detector.
135 The results of measurement expressed as percentage of injected dose per gram organ (blood in this case) (%ID/g) [x]
137- 139
In order to determine the biological half-life of 99mTc-MDP the %ID/g of blood samples plotted again time of their withdrawal.
Please Note:
Instead of biological half-time most articles use term of biological half-life
142- 144
It’s not clear what the meaning of this sentence is.
Is it t-test used to compare the biological half-life of 99mTc-MDP injected to mice in control group with treated group???
Need to be re-written.
145
Biodistribution study performed on normal animal group (I) and animal models group IV and V by injecting each mice with 0.1 mL of 99mTc-MDP (100 µCi) intravenously through the tail.
149- 158
Please do not use then as a subject of a sentence.
Mice were then euthanized 3 hours post injection and vital organs such as muscle, bone, blood, intestine, stomach, liver, spleen, kidneys, heart and lungs were taken. The collected samples weighed and then counted using single channel analyzer with Na(I)TL detector.
The %ID/g for each sample was then calculated.
163- 167
, vacumm….. What does is mean vacuum in this context???
__________________________________________________________________________
Radiochemical purity is one of quality requirements for a radiopharmaceutical in addition to clarity, sterility, non-pyrogenic and pH. Radiochemical purity in this study was performed using 2 ascending paper chromatography paper systems.
167 -
There is a miss-match between Figures and explanations.
Explanation Acetone (mobile phase) Figure Saline Explanation Saline (mobile phase) Figure Acetone
--- Figure 1 should be changed to Figure 2 and vice versa!!!
Fig.1 shows a radiochromatogram of 99mTc-MDP where acetone used as a mobile phase,
99mTcO2 and 99mTc-MDP stayed on origin (Rf = 0) while 99mTc-pertecnetate moved with the solvent to give an Rf of 1.
In Fig. 2 on the hand shows a radiochromatogram of 99mTc-MDP where saline solution (0.9% NaCl) used as a mobile phase, 99mTcO2 stayed at origin while 99mTc-MDP and 99mTc- pertecnetate moved with the solvent to give an Rf of 1.
174- 179
….respectively. This 99mTc-MDP conformed to the..
….radiochemical purity has to be greater than 95%.
179- 181
The solution of MDP dissolved easily in saline, giving a clear and colorless solution, 180
vacuum (???) and pH between 5.8 – 6.0.??? Not sure the meaning of this sentence
Do you mean “The MDP kits (???) dissolved easily in saline and gave a clear and colorless solution with pH of between 5.8 – 6.0.???. If yes,this sentence is not relevance as you were discussing 99mTc-MDP
Or
The solution of 99mTc-MDP is a clear and colorless with pH between 5.8 and 6.0. ???
182- 184
The blood clearance profile tests were performed in order to determine changes in pharmacokinetic profiles and biological half-life of 99mTc-MDP in mice which had been previously treated with meloxicam and natrium diclofenac.
184- The results in Fig. 3 …..
188- 192
….profile (%ID/g??) of 99mTc-MDP in blood of normal/ untreated (Group I), treated with meloxicam (Group II) and natrium diclofenac (Group III) mice 5 minutes post injection were 3.71, 8.96 and 9.15% respectively, then decrease to 0.12, 0.01, and 0.01% respectively 24 hours post injection.
--- Note:
To make the statement much clearer, use normal/ untreated (Group I), treated with meloxicam (Group II) and natrium diclofenac (Group III) mice instead of Group I, II and III. Ths is in line with expalanation on the graph (Fig. 3)
193- 195
Based on the calculation of %ID/ g of blood, biological half-life (distribution and elimination) can be determined as shown in Table.
--- Note:
1. The most common term used in biodistribution study is % ID/ g organ not radioactivity/ g organ.
2. Biological half-time is also not commonly used in biological study. Biological half- life is.
196
---showed there was no….in distribution 99mTc-MDP of in normal/ untreated mice (Group I) and in treated mice either with meloxicam (Group II) or natrium diclofenac (Group III).
However, there was significant difference in elimination of 99mTc-MDP in normal/ untreated mice (Group I) and in treated mice either with meloxicam (Group II) or natrium diclofenac (Group III).
200 - 205
To make the table to be easily read it is suggested to put some explanations/ legends as bellows:
Control/ Untreated mice (Group I) Treated with meloxicam (Group II)
Treated with natrium diclofenac (Group III).
208- 211
…medicine, bone scintigraphy using 99mTc-MDP usually performed 2-5 hours post injection for allowing a clearance of administered..……
213- 214
Biodistribution study (Fig. 4 and 5)…
…highest %ID/g organ was found in bone as the primary target of 99mTc-MDP radiopharmaceutical.
--- Be consistent!!
If you use Fig once use it all the time. Don’t use Fig and then Figure!!
216- 219
This sentences need to be re-written as it is not clear which data belong to Fig. 4 and which data belong to Fig 5.
__________________________________________________________________________
It can be seen from Fig 4 that the % ID/ g organ (bone) of 99mTc-MDP were XX ± XX, XX ± XX, XX ± XX, XX ± XX, XX ± XX% in control/ untreated mice (Group I)
etc……..respectively…….xx hours post injection.
It can be seen from Fig 5 that the % ID/ g organ (bone) of 99mTc-MDP were XX ± XX etc.
See the above-mentioned example!!!
219 - 230
This sentences need to be re-written!!!
…….respectively. It can be seen from these results that there were no significant different in bone uptake of 99mTc-MDP in mice with previously treated with meloxicam
………etc
231 99mTc-MDP bone uptake….
255 …99mTc-MDP bone uptake too.
319 -
323 Move Fig 2 to Fig 1 and vise versa
325- 327
Radioactivity (%ID/g) …should be only %ID/g”:
Suggested Legend change:
Normal Normal mice
Natrium Dicofenac Mice treated with Normal Meloxicam Mice treated with Meloxicam
329-
335 Same suggestion as line 325-335
