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Guidelines on nuclear medicine imaging in neuroblastoma

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Abstract

Nuclear medicine has a central role in the diagnosis, staging, response assessment and long-term follow-up of neuroblastoma, the most common solid extracranial tumour in children. These EANM guidelines include updated information on 123I-mIBG, the most common study in nuclear medicine for the evaluation of neuroblastoma, and on PET/CT imaging with 18F-FDG, 18F-DOPA and 68Ga-DOTA peptides. These PET/CT studies are increasingly employed in clinical practice. Indications, advantages and limitations are presented along with recommendations on study protocols, interpretation of findings and reporting results.

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Acknowledgments

These guidelines summarize the views of leading experts from the EANM and other continents and reflect recommendations for which the EANM cannot be held responsible. The recommendations should be considered in the context of good nuclear medicine practice and are not a substitute for national and international legal or regulatory provisions.

The guidelines were brought to the attention of all other EANM Committees and of the European National Societies of Nuclear Medicine. The comments and suggestions from the Oncology, Radiopharmacy and Technologist Committees and the Israeli, Belgian and Spanish National Societies are highly appreciated and have been considered for these guidelines.

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Authors

Corresponding author

Correspondence to Zvi Bar-Sever.

Ethics declarations

This article does not describe any studies with human participants or animals performed by any of the authors.

Conflicts of interest

Egesta Lopci declares that she received a grant for immunotherapy research, unrelated to these guidelines, from AIRC (Associazione Italiana per la Ricerca sul Cancro).

All other authors declare no conflicts of interest.

Additional information

Preamble

The European Association of Nuclear Medicine (EANM) is a professional nonprofit medical association that facilitates communication worldwide among individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985.

These guidelines are intended to assist practitioners in providing appropriate nuclear medicine care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care.

The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals taking into account the unique circumstances of each case. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set out in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines.

The practice of medicine involves not only the science but also the art of dealing with the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognized that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.

Appendices

Appendix 1

Drug interactions with mIBG

Extensive lists of medications with the theoretical potential to affect mIBG imaging have been previously published [36, 133, 134]. Several drugs listed in these publications are no longer commercially available. Moreover, the inclusion of drugs in these lists was based on the assumption that all drugs within a category could have the same effect on mIBG uptake as the drugs actually tested [54]. Medications that only indirectly affect circulating levels of norepinephrine, with an unknown specific mechanism of action, should not automatically be considered as likely to affect mIBG imaging results. This table presents the main categories of medications that can potentially affect mIBG uptake, with recommendations and comments regarding withdrawal based on the available evidence.

Category

Subcategory

Most commonly tested medication(s)

Level of evidencea

Strength of mIBG-inhibitory effect

Recommendations/comments

Drugs acting on adrenoreceptors

Beta blockers

Labetalol

Propranolol

High

Labetalol: strong

Others: none

Labetalol should be withheld

Others: withholding not required

Beta agonists

Salbutamol

Very low

None

Withdrawal not required

Alpha antagonists

Phenoxybenzamine

Low

Uncertain

Withdrawal probably not necessary

Alpha agonists

Clonidine

Very low

Uncertain

Withdrawal probably not necessary

Drugs affecting NE transport, retention or release

Tricyclic antidepressants

Desipramine

Medium

Moderate to strong

Should be withheld (otherwise, an alternative tracer for scanning should be considered)

SSRIs and SNRIs

Fluvoxamine

Low

Moderate to strong for some agents

Consider withholding agents with documented effect on NET

Other anti-depressants

Trazodone

Very low

None

Insufficient evidence for recommendation

NE depleters

Reserpine

High

Strong

If still in clinical use, should be withheld

Sympathomimetics

Phenylpropanolamine

Low

Strong

Should be withheld (otherwise, an alternative tracer for scanning should be considered)

Monoamines

Cocaine

Moderate

Moderate

In case of suspected use, screen patients prior to mIBG scan

Calcium channel blockers

 

Nifedipine

Cilnidipine

Medium

None

Effect (if any) is on release, not on mIBG uptake. Not necessary to withhold

Miscellaneous

Neuroleptics

Haloperidol

Very low

Uncertain

Uncertain

Anaesthetics

Ketamine

Xylazine

Pentobarbital

Very low

Uncertain

Uncertain

Cardiac glycosides

Digoxin

Very low

Uncertain

Uncertain; withdrawal probably not necessary

Antiarrhythmics

Amiodarone

Medium

None

Effect (if any) beneficial. Not necessary to withhold

  1. Modified with permission from [54]
  2. NE norepinephrine, NET norepinephrine transporter, SSRI selective serotonin reuptake inhibitor, SNRI serotonin-norepinephrine reuptake inhibitor
  3. aVery low one or two articles, low three or four articles, medium five to seven articles, high more than seven articles

Appendix 2

Thyroid blockade

  1. 1.

    123 I-mIBG

    1. (a)

      Potassium iodate tablets (doses according to the patient’s age; protocol in use at Great Ormond Street Hospital for Children, London, UK):

      • In a child between 1 month and 3 years of age: 42.5 mg (half a tablet) potassium iodate administered orally 1 h prior to mIBG injection, in the evening of that day, and on the following day after the mIBG scan (in total, three tablets in 2 days; in infants and young children the tablet can be crushed, dissolved in 2 mL of sterile water, and administered with a syringe to the back of the throat).

      • In a child between 3 and 12 years of age: 85 mg (one tablet) potassium iodate administered orally 1 h prior to mIBG injection, in the evening of that day, and on the following day after the mIBG scan (in total, three tablets in 2 days).

      • In patients above 12 years of age: 170 mg (two tablets) potassium iodate administered orally 1 h prior to mIBG injection, in the evening of that day, and on the following day after the mIBG scan (in total, three tablets in 2 days).

    2. (b)

      Lugol’s iodine solution:

      • Dose 0.6 mL of 5% solution per day.

      • Given orally 2 days before 123I-mIBG injection, and continued for 3 days after injection.

      • Should be diluted in any drink such as milk, or juice, as it may burn the throat if undiluted.

      • The dose can be given as a single dose each day or split into 2 × 0.3 mL doses.

  1. 2.

    131I-mIBG (in use at University Health Shreveport, Louisiana, USA):

    1. (a)

      Protocol of administration: saturated solution of potassium iodide (SSKI) 30–60 min prior to injection of 131I-mIBG, orally from day 0, continued for a week.

    2. (b)

      Dosage:

      • Adult dosage: six drops of SSKI on day 0 and two drops of SSKI three times a day orally, beginning on the morning of day 1 and continuing for 1 week.

      • Paediatric dosage:

        <1 month: one drop orally 30–60 min prior to 131I-mIBG injection, then one drop orally in the morning of day 1, and daily for 1 week following injection.

        1 month to 3 years: two drops orally 30–60 min prior to 131I-mIBG injection, then one drop orally twice a day beginning in the morning of day 1 and continuing for 1 week following injection.

        3 to 18 years: three drops orally 30–60 min prior to 131I-mIBG injection, then one drop orally three times a day beginning in the morning of day 1 and continuing for 1 week following injection.

        ≥70 kg to adult: six drops orally 30–60 min after 131I-mIBG injection, then two drops orally three times a day beginning in the morning of day 1 and continuing for 1 week following injection.

  2. 3.

    Potassium perchlorate: in individuals sensitive to iodine, and if no other method for thyroid blockade is available.

    Dose 10 mg/kg (maximum dose 500 mg, minimum dose 50 mg). Potassium perchlorate comes in 200 mg capsules and these should be opened and the contents either placed on a sugar lump (or similar) or dissolved in a flavoured drink. Potassium perchlorate is taken 1 h prior to 123I-mIBG injection and up to five times in the following 36 h.

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Bar-Sever, Z., Biassoni, L., Shulkin, B. et al. Guidelines on nuclear medicine imaging in neuroblastoma. Eur J Nucl Med Mol Imaging 45, 2009–2024 (2018). https://doi.org/10.1007/s00259-018-4070-8

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