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ATOM INDONESIA

Author's Responses

Article : #741

Article Title : Pharmacokinetics Interaction of Non-Steroid Anti Inflammatory Drugs with

99mTc-MDP Radiopharmaceuticals for Bone Imaging

Line # Referee’s Comments Author's Responses

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Blood samples were withdrawn from each mouse which were then weighted and counted using single channel analyzer.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.

The injected dose is 100 µCi/100 µL

16-25 It’s suggested to be removed. It’s unnecessary

statement. Already revised

33 …compounds such as… Already revised

71 Remove The. Materials used… Already revised

74 …HCl dan acetone (E. Merck), NaCl 0.9%,

aquabidest (IPHA) Already revised

76 …3MM Whatman chromatography paper Already revised 78 …(Merck). In-house prepared MDP

radiopharmaceuticals kits. Already revised

84-90 These lines should be deleted. There are

duplications (see previous lines)!!! Already revised

93 All steps Already revised

(2)

93-96

Please do not use number as a subject of a sen- tence!!!

99mTc-Pertecnetate (3 mL, 3 mCi) was added into vial containing MDP kit.

Already revised

96 he solution was shook…..at room temperature re-

sulted in 99mTc-MDP radiopharmaceutical. Already revised

99

Radiochemical purity of 99mTc-MDP was determined using 2 paper chromatography system. 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]

Already revised

108- 109

This research….. This sentence is suggested to be

removed. It’s unnecessary statement Already revised

115 …except in… Already revised

125 …test used… Already revised

128 and III. The treated mice were injected with

….injected through their tail veins Already revised

130 At specified time…. Already revised

132- 134

...99mTc-MDP, blood samples were withdrawn from the tail of each mouse. Blood samples were then weighted and counted using …single chan- nel analyzer Na(I)Tl detector.

Already revised

135

The results of measurement expressed as percent- age of injected dose per gram organ (blood in this case) (%ID/g) [x]

Already revised

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

Already revised

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.

Already revised

145

Biodistribution study performed on normal ani- mal 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.

Already revised

149- 158

Please do not use then as a subject of a sentence.

Mice were then euthanized 3 hours post injection

Already revised

(3)

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 require- ments for a radiopharmaceutical in addition to clarity, sterility, non-pyrogenic and pH. Radio- chemical purity in this study was performed using 2 ascending paper chromatography paper sys- tems.

Already revised

167-

There is a miss-match between Figures and expla- nations.

Explanation Acetone (mobile phase)  Figure Saline

Explanation Saline (mobile phase)  Figure Ace- tone

--- --- 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.

Already revised

174- 179

….respectively. This 99mTc-MDP conformed to the..

….radiochemical purity has to be greater than 95%.

Already revised 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 eas- ily 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

Already revised

(4)

Or

The solution of 99mTc-MDP is a clear and color- less 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.

Already revised

184- The results in Fig. 3 ….. Already revised

188- 192

….profile (%ID/g??) of 99mTc-MDP in blood of normal/ untreated (Group I), treated with meloxi- cam (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 injec- tion.

--- ---

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 explanation on the graph (Fig. 3)

Already revised

193- 195

Based on the calculation of %ID/ g of blood, bio- logical 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.

Already revised

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).

Already revised

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).

Already revised

208- 211

…medicine, bone scintigraphy using 99mTc-MDP usually performed 2-5 hours post injection for al- lowing a clearance of administered..……

Already revised 213-

214

Biodistribution study (Fig. 4 and 5)…

…highest %ID/g organ was found in bone as the

Already revised

(5)

primary target of 99mTc-MDP radiopharmaceuti- cal.

--- ---

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 injec- tion.

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!!!

Already revised

219- 230

This sentences need to be re-written!!!

…….respectively. It can be seen from these re- sults that there were no significant different in bone uptake of 99mTc-MDP in mice with previ- ously treated with meloxicam………etc

Already revised

231 99mTc-MDP bone uptake…. Already revised

255 …99mTc-MDP bone uptake too. Already revised 319-

323 Move Fig 2 to Fig 1 and vise versa Already revised

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

Already revised

329-

335 Same suggestion as line 325-335 Already revised

Please return to Atom Indonesia Editorial Office via supplementary file in OJS aplication.

6/6/2018

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