CSF-1R ultrasound molecular imaging for noninvasive diagnosis of hepatocarcinoma
Recently published study explores the use of CSF-1R-targeting ultrasound imaging for diagnosis of hepatocarcinoma. We interviewed Dr Qiongchao Jiang, the first author of the study, to get insights on the background and significance of this newly developed diagnostic approach.
Can you shortly present yourself to our audience?
Dr Jiang: My name is Qiongchao Jiang, the first author of this paper. I am a medical doctor who specialized in ultrasound imaging. I have been working in the Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University (China) for more than 6 years. I have just been promoted to the position of Associate Professor. First of all, allow me to graciously thank you for extending this invitation for a chance to be interviewed for our publication. I am very honored to share my personal experience on this publication.
What are the diagnostic advantages of monitoring CSF-1R and what were the existing challenges that your work aimed to address?
Dr Jiang: To completely answer this question, we need to first of all understand the underlying reason of radiofrequency ablation (RFA). RFA is a minimally invasive technique that shrinks the size of tumors, nodules or other growths in the body. In order to achieve the complete RFA, it is vital that we know exactly where the tumor margin is. Without this knowledge, RFA could not be complete, which leads to the term ‘incomplete RFA’ or IRFA. Most, if not all current RFA has the probability of IRFA due to the lack of standard method in determining tumor margin. Even with the most experienced ultrasound doctor, personal bias could lead to the wrong determination of tumor margin. Therefore, there is an urgent need to develop an ultrasound-guided method. We found that CSF-1R is highly localized in the tumor margin of liver cancer and these receptors are co-localized with tumor-associated macrophages (TAMs). This observation leads us to develop a CSF-1R target nanobubbles (NBs) that could bind to the TAMs, which we now know to be preferably situated at boundary of the tumor. Therefore, taking the advantage of targeting TAMs and CSF-1R is a method of killing two birds with one stone. On the one hand, we could clearly determine the margin of the tumor and on the other hand using ultrasound contrast agent can increase visibility of targeted area for complete RFA.
However, we do acknowledge that this work is still preliminary and many challenges remain. For one, we need to understand the tumor microenvironment of different tumors and whether TAMs are present in all boundaries. Second, the specific targeting of the NBs used in carrying the ultrasound contrast agent should be optimized to increase tumor/liver ratio and decrease their nonspecific targeting towards other organs in vivo. Third, the reproducibility of these NBs in case of clinical translation requires GMP standard and strict regulation, which is still a question mark for us.
How challenging was the work on the development and validation of the new diagnostic approach? Were there some steps that proved to be especially difficult or unexpectedly easy?
Dr Jiang: I believe this question is of relevance for all research. No development and validation of new diagnostic approach is easy. Personally, I think all of research work is challenging. However, having said that, the most challenging part for me is to realize the hypothesis from the stage of an idea to a product. Having no experience in lab work, I was struggling with the development of NBs. I was very fortunate to have full support of our colleagues and friends, who gave me a lot of help and encouragement along the way. The step that I found most difficult in this project was to create a consistent NBs with optimal targeting properties. The other difficult part was to identify highly specific target that is ONLY present in the target cells. For example, HER-2 could be used as a good target because it is highly expressed in breast cancer and not in other organs. Therefore, for us to develop a clinically-relevant targeting and diagnostic agent, the target of choice is of utmost importance. Creating something from scratch is no easy task. One needs a lot of patience and persistence to make it work. And needless to say, nothing comes easy in the process, but I have learnt to persevere. My advice to the younger generation scientist is; be prepared to tough it up, but the end is worth it.
What are the strengths of the newly developed diagnostic approach and are there some down-sides of using it? How does it compare to other existing diagnostic alternatives?
Dr Jiang: From my experience, our NBs possess higher stability (longer blood retention time and longer tumor retention time) as compared to clinically used Sonovue or Sonozid. This could prove to be useful in patients needing a longer ultrasound time or during RFA. However, we also observe some immune reactions with repeated dosage of NBs, which might be attributed to the lipids and peptides in the NBs. We are now working to optimize these NBs to create a second generation of NBs retaining all the positive attributes, but with minimal in vivo toxicity/immune response.
What are the most important potential future applications of the new diagnostic approach?
Dr Jiang: In my opinion, I can foresee that using our NBs, we can accurately identify the margin of hepatocarcinoma (we also have similar findings in breast cancer, an unpublished result) to improve the efficacy of RFA in the clinics.
What are your further work directions?
Dr Jiang: Our ultimate goal is to develop smart NBs that could integrate various modalities in one system for simultaneous diagnosis and therapy.
Considering the overall recent scientific and technological advances, what are your forecasts for future developments and applications in this area?
Dr Jiang: From a patient’s point-of-view, ultrasound is a safe and cheaper imaging modality (compared to MRI and CT scanning). Combining the fact that RFA is a minimally invasive procedure, these could be widely used procedures in the future. Therefore, I believe that the development of diagnostic materials for US-guided RFA could be widely used in the clinics in the near future.
For our readers who are interested to learn more about the discussed topics – would you like to recommend some valuable sources for obtaining further information?
Dr Jiang: There are many informative resources on RFA, US-guided RFA, targeted therapy, NBs; published elsewhere. I strongly suggest readers to broaden their mind by reading more papers beyond their research scope. By doing this, one will have new ideas, which come from integrating various topics to create a paradigm shift in their field.
Interviewer: Atanas G Atanasov, research leader focusing on molecular medicine and digital health, PI of LBI-DHPS, Editor-in-Chief of CRBIOTECH, and Executive Administrator of the open innovation platforms DHPSP and INPST. Social media contacts: Twitter, LinkedIn, Facebook.
The opinions expressed in this feature are those of the author and do not necessarily reflect the views of Bioanalysis Zone or Future Science Group.
