Fachverband für Strahlenschutz e. V. - represented by its Medical Radiation Protection Working Group
The ICRP recommendation provides a good overview of the technology, indications and radiation protection of PET, PET/MR and PET/CT. The fact that quality assurance and patient safety management measures are listed in the manuscript should also be emphasized as especially positive. Chapter 5.3 (Justification) is also especially well written and requires no comment.
However, it seems that there are some comments and clarifications that need to be made. Below are some comments that may help to improve the forthcoming publication. Lines in the manuscript are referenced below. Where appropriate, relevant literature is listed.
General comments:
A consistent spelling of PET/MRI and PET/MR should be used throughout the manuscript, and writing PET/MR is recommended.
The bladder dose is discussed in several chapters and at the same time measures for reduction are listed. It should be considered whether these recommendations could be brought together in one chapter and referenced there.
One publication is the main source of information on activities applicable to newer PET tracers. For this comment, we analyzed over 5000 PET scan datasets with newer tracers (PSMA, DOTA-TOC, CPCR4, FAPI) from several centers using 3 different PET systems. The results are attached below.
131, 1632
For some examinations, especially for examinations with FDG, it is necessary for the patient to rest after the injection. In the above lines, however, the text seems to imply that this rule of conduct applies to all PET tracers, which is not the case.
172/173, 199, 248
Especially in the Main Points as well as in the Executive Summary, the importance of CT is not always correctly presented in the context of PET. The presentation in line 247 ff. and 1585 ff. is correct. In contrast, CT is only mentioned in line 199 alongside MRI for better anatomical visualization. In line 172 f., a technical objective should therefore be considered in addition to the clinical objective.
314, 327, 330, 1148, 1496, 3249
First, it is important to note that 68-Ga is not only available as a generator product; rather, it should be taken into account that 68-Ga is also increasingly available as a cyclotron product. 124-I, 89-Zr, 64-Cu should be considered as regularly clinically used nuclides. In post-therapeutic imaging, e.g. after TARE, 90-Y PET plays an important role due to its quantifiability and better resolution.
574
In addition to PET and PET/CT, PET/MR should also be mentioned here.
606
PET also has an important role in inflammation diagnostics, as already correctly described in line 513.
655
Iodine (124-I) is another important biological element in addition to those mentioned and plays a role in the diagnosis of thyroid cancer and metastases with PET.
707
The blue background makes it difficult to read the figure and in my printout the figure is displayed with low resolution.
1069-1076:
Minoshima et. al. quantified cerebral glucose metabolism using FDG-PET at the middle of the 1990s. At that time, the method was already being developed for clinical application. For many years now, FDG-PET has played an important role in the diagnosis and differentiation of neurodegenerative diseases, not only in the diagnosis of Alzheimer's disease. Quantitative evaluation of metabolism plays a central role in the procedure.
1109-1117:
When discussing individual oncological PET tracers, not only the two most frequently used tracers should be considered, but all the main tracers that have found their way into clinical routine.
For some years now, imaging with chemokine receptor 4-directed ligands has played an increasingly important role in PET imaging and the theranostics of hematologic diseases.
Gastrin releasing peptide receptor-directed imaging is already playing an increasingly important role in the diagnosis and treatment of prostate cancer.
Further peptide probes based on the natural ligands minigastrin (MG) and cholecystokinin (CCK) have high potential for molecular imaging and targeted radiotherapy of different human tumors, such as medullary thyroid carcinoma (MTC) and small cell lung cancer (SCLC).
Tracers have also been developed for tumors that were previously only accessible to FDG-PET to a limited extent, e.g. glypican 3 for the diagnosis and treatment of hepatocellular carcinoma.
In epithelial neoplasms Fibroblast activation protein-α (FAPα) is overexpressed on cancer-associated fibroblasts. Corresponding PET tracers have been developed as FAP inhibitors (FAPI).
1057-1118, 2389, 2414
With a rapidly growing body of evidence, it is increasingly recognized that FDG PET/CT has clinical utility in suspected infection and inflammation, in addition to its established role in oncologic imaging. It can identify the source of infection or inflammation before morphological changes on conventional anatomical imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI), map disease extent and severity, identify sites for tissue sampling, and assess response to therapy. FDG-PET can also be used as a systematic diagnostic tool for rheumatic diseases. Other tracers such as DOTA-conjugated somatostatin analogs and CXCR4-directed tracers can also be used in infection diagnostics.
It should therefore be considered whether a section 2.6.4 on inflammation diagnostics should be added.
1616-1659; 1749-1754
The PET patient's journey through the facility is carried out, for example, during an examination with FDG. This should also be better emphasized in line 1622, as the following lines also describe fasting before the examination, for example. However, these behaviors are very specific and for individual questions with FDG, e.g. longer fasting intervals or further preparation of the patient (e.g. special diet on the days before the examination) are required, so that consideration should be given to formulating Chapter 3.5 in more general terms.
2543
PET and PET/CT should be listed here, as is the case in line 2549.
2687-2688
The statement regarding the use of a diagnostic CT for attenuation correction is absolutely correct. Nevertheless, this statement should be substantiated with available literature.
2846-2847
It should be noted that Table 6.4 is based on the publication ARSAC, 2021. However, several tracers are not included in this comprehensive table that have found their way into clinical practice. Firstly, an 18-F-PSMA tracer has now been approved in some countries and others are in the process of being approved; with these tracers, the activity per kilogram of the patient's body weight is usually determined; For 18-F-PSMA 4 MBq per kg body weight is currently the norm. The 68-Ga-PSMA tracer, which has already been approved in many countries some time ago, was approved with a corridor of 1.8-2.2 MBq per kg body weight and a minimum activity of 111 MBq. A corridor of 100-200 MBq per patient and examination is also specified in the approval for the approved tracer 68-Ga-DOTA-TOC; here the DRL specified in Table 6.4 appears to be clearly too high. In addition, the activity for these tracers should be defined as MBq/kgBW. Other tracers regularly used in clinical routine, such as 68-Ga-CPCR4 (CXCR4), have not yet been taken into account. It is therefore proposed that the table created on the basis of ARSAC 2021 be supplemented with data from clinical care reality, in particular to add activity by weight information on 18-F-PSMA, 68-Ga-PSMA, 68-Ga-DOTA-NOC/TOC/TATE, 68-Ga-CPCR4/CXCR4, and 68-Ga-FAPI.
To provide a sense of clinical reality and real-world data, unpublished data from PET centers with a total of 3 PET systems (Siemens Biograph 40 mCT, Siemens mCT Flow, GE Discovery MI, purchase period 2012-2023) evaluated over 3 years are listed below, along with examination frequency.
|
Tracer |
No of Scans |
Mean MBq/kgBW |
Median MBq/kgBW |
Max MBq/kgBW |
Min MBq/kgBW |
SD |
|
18-F-PSMA |
3172 |
4,0 |
4,0 |
6,2 |
1,4 |
0,3 |
|
68-Ga-PSMA |
1563 |
1,4 |
1,3 |
2,8 |
0,6 |
0,3 |
|
68-Ga-DOTA-TOC |
434 |
1,6 |
1,6 |
3,0 |
0,7 |
0,4 |
|
68-Ga-CPCR4 |
74 |
2,0 |
2,0 |
3,3 |
1,1 |
0,5 |
|
68-Ga-FAPI |
60 |
2,2 |
2,2 |
3,5 |
1,3 |
0,5 |
From the point of view of radiation protection for the patient, lower activities per kgBW should be used as long as the image quality and measurement time are acceptable. The evaluation shows that these lower activities, especially for 68-Ga-tracers, can be used in daily clinical practice. A range of 1.8-2.0 MBq/kgBW seems to be completely sufficient even for older PET scanners.
2902
The values in the table are difficult to read due to the fact that they are not placed directly below each other.
3038-3100
The revision of Pub 62 should be taken into account in this chapter. LNT should also be discussed (lines 3092-3095)