Discussion:
COVID-19 pandemic has posed many unanticipated and unprecedented
challenges in healthcare worldwide, including cancer
patients16. Prior to the pandemic, establishing cancer
diagnosis and carrying out the standard staging investigation was not
seen to be a potential problem for oncology and nuclear medicine
departments, especially in high-income countries. Faced with the
logistic difficulty of 123I-MIBG procurement, we
decided to perform 68Ga-DOTATATE PET/CT scans, in the
presence of limited but compelling evidence of its utility for initial
staging of Neuroblastoma. Our results will add to the evidence base for
future studies.
68Ga-DOTATATE scans in our patients showed a very high
spatial resolution and high accuracy quite concordant with reports in
literature 8, 15, 17. Although direct comparison with
MIBG was not possible, functional information and detection rate was
higher than concurrent anatomical imaging.
In Neuroblastoma management, the role of MIBG scintigraphy is not only
in staging and response evaluation, presence of MIBG avid disease at
diagnosis also predicts response to therapy and persistence of disease
after induction chemotherapy is indicative of a poor prognosis18, 19. However, it is also associated with several
logistic disadvantages. In addition to the lengthy process of acquiring
the radiopharmaceutical, imaging is carried out at least 24 hours after
its administration. Children may require inpatient admission and must
repeatedly visit the nuclear medicine department. Also, MIBG can result
in the accumulation of unbound Iodine in the thyroid gland.
Administration of Lugol’s solution is therefore required for adequate
thyroid blockade. Finally, MIBG uptake is affected by other seemingly
innocuous medications that can affect MIBG uptake and result in poor
sensitivity and accuracy of the study 20, 21. Imaging
with single-photon emission computerized tomography SPECT-CT requires
some logistical and software enhancements in order to achieve a similar
whole body acquisition as the PET-CT study. On the other hand68Ga-DOTATATE can be produced locally by using a
generator and the patient is injected and imaged on the same day.
Additionally, no special preparation is required other than avoiding
somatostatin analogues.
Role of 68Ga-DOTATATE PET/CT has previously been
studied at the time of recurrence and at the therapeutic planning phase
within a theranostics paradigm. However, there are very few reports of
its role at diagnosis for staging8, 15. Maurice et al
found that in their series of 15 adults with pheochromocytoma and
paraganglioma, 68Ga-DOTATATE was positive in 5
patients where MIBG was negative, whereas converse was true for only 2
patients 22. Similarly Naji et al found that in adults
with Neural crest tumors, 68Ga-DOTATATE showed 10 out
of 12 lesions, vs. 5 shown by MIBG23. There is a
paucity of data in combined MIBG scintigraphy and PET/CT DOTATATE
emission tomography. Krois et al compared the sensitivity and
specificity of 68Ga-DOTATATE to MIBG and morphological
imaging in their series of 11 patients (mixed pediatric and adult
cohort). Although, only 5 of 11 patients had a diagnosis of
Neuroblastoma, DOTATATE sensitivity was 97% vs 90% for
MIBG8. In a case report, Agarwal et al reported the
utility of 68Ga-DOTATATE PET/CT in diagnosis and
response evaluation in a 12 year old child with
Neuroblastoma15.
Two of the three patients undergoing gallium imaging had metastatic
disease evaluable on morphological imaging and bone marrow evaluation.
All lesions evaluable on MR scans were also avid on68Ga-DOTATATE PET/CT imaging affirming the hypothesis
that it is highly sensitive for Neuroblastoma.
The effective radiation doses for 123I-MIBG and68Ga-DOTATATE are 0.013 mSv/MBq and 0.021 mSv/MBq
respectively24, 25. Depending on the activity schedule
for a 20 kg pediatric patient using the standardized EANM weight-based
activity calculator26, (62 MBq for68Ga-DOTATATE and 136 MBq for123I-MIBG) an approximate 25% radiation dose saving
can be made with the use of 68Ga-DOTATATE, based on
the assumption that a similar low dose CT is performed in both
studies17, 24-27.
68Ga-DOTATATE PET-CT has clear advantages compared to123I-MIBG scintigraphy, with the latter suffering from
low image quality, difficulties in image quantification, and poor
spatial resolution of SPECT (up to 1 cm using medium energy collimators)
as well as thyroid blockade and discontinuation of certain medications.
PET presents inherent advantages with better spatial resolution (4-5 mm)
even with a relatively large positron energy of 1.9 MeV, quantified
images in kBq/ml. Practical advantages also include more rapid imaging
requiring less sedation as well as no specific patient preparation
requirements.