The present study found that delayed phase 123I-IMP SPECT was the most useful imaging examination for differentiation between PCNSL and GBM, compared with early phase 123I-IMP SPECT, early and delayed phase 201Tl SPECT, and ADCmean and ADCmin on MR imaging. 201Tl SPECT was less useful for differentiation compared with 123I-IMP SPECT. However, high RI was helpful to estimate the extent of the malignant tumor. T/N ratio of 201Tl SPECT was higher than that of 123I-IMP SPECT, which was helpful to establish the tumor localization.
The imaging characteristics of PCNSL are homogeneous enhancement, and multiple lesions in 34-58% of cases [29-31]. However, ring-like enhancement occurs in 25% of PCNSL, and multiple lesions occur in 10-20% of GBM , so preoperative discrimination between PCNSL and GBM are still controversy on preoperative conventional MR imaging.
ADC value on MR imaging is reported to be useful for the diagnosis of brain tumor. ADC value of PCNSL is lower than that of GBM reflecting the higher cellular density [3-6]. The best sensitivity and specificity for differentiation between PCNSL and GBM are 85% and 90%, respectively . However, recent studies showed sensitivity and specificity are about 70% [3,4], indicating that ADC is not sufficiently accurate to diagnose these tumors. Our study also found that ADC value was valuable, but relatively less effective to differentiate these tumors.
PCNSL is reported to uptake more FDG than GBM . The cut-off value and the accuracy vary, but the diagnostic accuracy of [18F]FDG PET was sensitivity 100% and specificity 71.4%, and sensitivity 84.2% and specificity 84.1% with the cut-off value 12 [7,8]. [18F]FDG PET is also useful for the staging of lymphoma due to its ability to evaluate systemic lesions . However, [18F]FDG PET is affected by blood glucose level, steroid administration, and previous radiation therapy . [18F]FDG must be produced in a cyclotron, so may not be available in all institutions .
Our study revealed that 123I-IMP SPECT can differentiate between PCNSL and GBM with higher accuracy than ADC and is comparable to [18F]FDG PET. IMP is a lipophilic tracer, so is permeable to the blood-brain barrier and correlates with cerebral blood flow . IMP shows high first-pass uptake by brain tissues with nonspecific amine binding sites and reveals slow washout . Transient accumulation in the early phase is considered to reflect blood flow, blood pooling, and pH in the tissue [25, 35, 36, 39]. Some brain tumors with high early IMP uptake, including meningiomas, metastatic brain tumors, lymphoma, and gliomas in the early phase have been reported . Dynamic SPECT scan studies have revealed that these accumulations resulted from intravascular retention of 123I-IMP .
One the other hand, the mechanisms of 123I-IMP accumulation on delayed phase remain to be elucidated. Delayed SPECT images may reflect the distribution of hydrophilic metabolites of IMP resulting from further oxidation of the aliphatic side chain . In addition to PCNSL, delayed PCNSL, delayed IMP acculmation had been reported in cellular blue nevus, and cartinoid [36,37]. These tumors express abundant amine-binding receptor to produce melanin or mono amine. 123I-IMP may be retained over delayed phase by binding to amine-binding receptor [25,36,37]. IMP accumulates in malignant lymphoma specifically in delayed phase, so is expected to be useful to diagnose PCNSL [24-26]. In our results, delayed phase 123I-IMP SPECT showed the highest AUC for differentiation between PCNSL and GBM among several imaging results. Delayed phase 123I-IMP accumulation on SPECT could be an important preoperative marker for predicting PCNSL, as other brain tumors with delayed IMP retention are less frequent.
201Thallium is the most commonly used tracer to evaluate tumors. Uptake of 201Tl is considered to reflect proliferation of tumor and blood flow, so uptake and retention are correlated with the malignant characteristics of the tumors [15-20, 40, 44 41]. Therefore, 201Tl SPECT is reported to be useful to estimate the malignancy of tumors and differentiate between tumor recurrence and radiation necrosis [21-23]. The present study revealed that 201Tl SPECT was inferior to 123I-IMP SPECT for differentiation between PCNSL and GBM, as 50/52 cases (96.2%) showed RI over 0.7, which is considered to indicate malignant tumor , and was useful to estimate the malignancy of tumors. 201Tl SPECT is also superior to 123I-IMP SPECT for estimating the localization of the tumor due to its higher T/N ratio.
SPECT can simultaneously image two isotopes with different energy windows [42,43]. Since the mechanisms of uptake into tumors are different depending on the isotopes, simultaneous injection of dual isotopes is expected to improve diagnostic accuracy and efficiency. Drug resistance of brain tumors could be estimated by technetium-99m methoxy-2-isobutylisonitrile SPECT in addition to 201Tl SPECT . The lipophilic tracer technetium-99m hexamethylpropyleneamine oxime could estimate tumor invasion and differentiate between tumor recurrence and radiation necrosis even in tumor with low uptake of 201Tl [43,44]. The present study revealed that 201Tl SPECT is useful for diagnosis of malignant tumor, and 123I-IMP SPECT is useful for differentiation between PCNSL and GBM. In the clinical setting, 123I-IMP and 201Tl SPECT can differentiate between malignant tumors and non-neoplastic lesion, between malignant tumors and benign tumors, and between PCNSL and GBM at the same time. Dual isotope 123I-IMP and 201Tl SPECT are useful and efficient for the preoperative diagnosis of PCNSL and GBM.