Lakhasly

The choice of patients groups will benefit more from certain drug is very critical step in treatment success and reduce the toxicity and cost.Refinement : this principle is applied since they used noninvasive in vivo PET imaging The radiation exposure to the NSCLG was limited with safety with minimum adverse effectsOverall in my opinion the animals models selection was perfect and the NSCLC patients are good choices but there are a lots of things can be modified such as the sample size and randomaiztion to prevent baise and maybe to be more specific and accurate more studies on Non-rodent species is needed before clinical trials since Non-rodent species is more close to human physiology and bigger than Rodents since the size of the animals models consider as important factor.Both studies was mentioned the ethical approval and compliance with regulations and ethics The preclinical trial on animals supports the authors' conclusions which is demonstrated the ability to use a noninvasive immunotherapeutic-based imaging agent to monitor PD-1 localization and expression in vivo , and its statistically significant since the p-value less than 0.05 so there's a real uptake of the radiolabel drug by tissue.The clinical trial on NSCLC patients the 89Zr-pembrolizumab uptake was safe and that it was higher in patients with a response than in patients without a response, but this fnding was not statistically signicant due to small sample size so further studies are needed

Replacement : this principle is not applied , since they used Humanized animal models ( mice and rats ) , I think the use of animals model is necessary to test the biodistribution, pharmacokinetics, and dosimetry in vivo and can't be replaced by other test such as vitro assays or in silico studies Reduction : no clear number of animals used but they mentioned the use of 4 animals in each.

The choice of patients groups will benefit more from certain drug is very critical step in treatment success and reduce the toxicity and cost. The current method of selecting patients for single-agent treatment with pembrolizumab by using immunohistochemistry not enough since some patients respond and the other not. So Another method is needed to investigate which type of patients will benefit more.
Researchers star the first clinical trial that aim to study the safety of administration of 89Zr-pembrolizumab in NSCLC patients to assess the biodistribution and to correlates the tracer uptake with PD-1 and PD-L1 immunohistochemistry and the response to pembrolizumab treatment.This will help in the selection of patients who will bene t the most.
This study is supported by previous study which is concluded, rodents provide evidence showed that 89Zr-Df-pembrolizumab is appropriate for tracking the fate of pembrolizumab in vivo.

The choice of animals model was logical for me, according to the 1st study the use of Humanization of models which immunode cient mice are engrafted with human cells or tissues is very useful and support the preclinical and clinical translation and mimic the human immune system.
Also, the choice of animal species which is Rodents( mice and rats) was made sense since they are inexpensive and well-characterized genetically, and are suitable for many pharmacokinetic which is the aim of researchers to study the biodistribution and pharmacokinetics.

The choice of NSCLC patients in the clinical trial make sense, since this type of cancer patients appeared to have a high expression of PD-1 which is the target of pembrolizumab. The principle of blinding is applied since unaware experienced thoracic pathologist evaluate the slide of tumor biopsies before the administration of 89Zr-pembrolizumab .The sample size was 12 which is very small, and there was a lack of randomization and a control group but so further studies with a large sample size are needed to rely on the results and generalise the outcome.
Overall in my opinion the animals models selection was perfect and the NSCLC patients are good choices but there are a lots of things can be modified such as the sample size and randomaiztion to prevent baise and maybe to be more specific and accurate more studies on Non-rodent species is needed before clinical trials since Non-rodent species is more close to human physiology and bigger than Rodents since the size of the animals models consider as important factor.Both studies was mentioned the ethical approval and compliance with regulations and ethics
The preclinical trial on animals supports the authors’ conclusions which is demonstrated the ability to use a noninvasive immunotherapeutic-based imaging agent to monitor PD-1 localization and expression in vivo , and its statistically significant since the p-value less than 0.05 so there’s a real uptake of the radiolabel drug by tissue.
The clinical trial on NSCLC patients the 89Zr-pembrolizumab uptake was safe and that it was higher in patients with a response than in patients without a response, but this fnding was not statistically signicant due to small sample size so further studies are needed

Replacement : this principle is not applied , since they used Humanized animal models ( mice and rats ) , I think the use of animals model is necessary to test the biodistribution, pharmacokinetics, and dosimetry in vivo and can’t be replaced by other test such as vitro assays or in silico studies
Reduction : no clear number of animals used but they mentioned the use of 4 animals in each.
Refinement : this principle is applied since they used noninvasive in vivo PET imaging
The radiation exposure to the NSCLG was limited with safety with minimum adverse effects