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.