An elderly male with a neuroendocrine tumor (NET) and liver metastases underwent peptide receptor radionuclide therapy (PRRT). Approximately 7.7 GBq (200 mCi) of 177Lu DOTATATE with concurrent amino acid infusion was administered by intravenous (IV) infusion. A SPECT/CT acquisition was performed 4 hours after the therapy infusion. Subsequent sequential SPECT/CT acquisitions were also acquired at 24-hours, 96-hours, and 168-hours post therapy.
The study was conducted on Symbia Pro.spectaTM[a] SPECT/CT, which was calibrated for 177Lu absolute quantification using xSPECT Quant’s National Institute of Standards and Technology (NIST)-traceable Selenium 75 (75Se) medium-energy calibration source. Following the initial low-dose CT, a SPECT acquisition using a medium-energy low-penetration (MELP) collimator was performed at 60 views per detector with a 20-second acquisition per view. The study was acquired for 2 bed positions in order to obtain both the thorax and abdomen, although the focus was primarily on the liver and kidney tracer concentrations.
xSPECT QuantTM reconstructions (128 x 128 matrix, xSPECTEM 24i4s) were subsequently performed using the SPECT and CT data. xSPECT Quant data across multiple timepoints was reviewed on syngo®.via to estimate lesion and critical organ tracer concentration in Bq/ml.
Figure 1: Sequential SPECT/CT with xSPECT Quant performed at 4 hours, 24 hours, 96 hours, and 168 hours following a therapy dose of 7.7 GBq (200 mCi) of 177Lu DOTATATE in a patient with a metastatic NET and multiple liver metastases shows a gradual increase in tracer concentration in the liver lesions with the peak at 24 hours and slow washout shown on the 168-hour study. Renal cortical tracer concentration shows initial high uptake with progressive washout.
Figures 1 and 2 show maximum intensity projection (MIP) and multiplanar reconstruction (MPR) views of sequential SPECT/CT studies, which demonstrate an initial high uptake of 177Lu DOTATATE within multiple liver metastases with a progressive increase in uptake between 4 hours and 24 hours. The 24-hour study shows the highest lesion uptake with subsequent slow washout revealed on the 96- and 168-hour studies. However, a significant amount of retained tracer is still visualized within the largest liver metastases even at 168 hours post-therapy administration. On the contrary, the bilateral renal cortex shows normal thickness and high initial tracer uptake but with progressive washout. There is slow clearance of tracer between 4 hours and 24 hours in the renal cortex but with faster clearance and low renal tracer uptake at 168 hours. This visual impression suggests prolonged retention of the radionuclide within the liver metastases and fast tracer transit with fast washout in the renal cortex. This implies the possibility of high absorbed dose to the liver metastases due to the longer tracer retention following radionuclide therapy but low renal cortical absorbed dose due to fast clearance.
As shown by the quantitative evaluation of tracer concentration in liver metastases by sequential xSPECT Quant studies (Figure 3), there is an increase in tracer concentration between 4 hours and 24 hours with the maximum reached at 24 hours with slow washout. Tracer retention within liver lesions at 168 hours is approximately 35% of the maximum concentration achieved at 24 hours. However, the renal clearance is rapid with maximum concentration in the renal cortex achieved by 4 hours with progressive clearance with less than 20% of the maximum concentration remaining at 168 hours.
xSPECT Quant and CT DICOM data were transferred to third-party dosimetry software[b] for calculation of absorbed dose. Tracer concentration values from 4 time points were used to generate time-activity curves (TACs) for every voxel followed by dose calculation using a linear Boltzmann transport equation (LBTE) solver. LBTE simulates an infinite number of radiation particles interacting with the heterogeneous media. CT and SPECT images across multiple timepoints were aligned and the automatic segmentation of the critical organs—lungs, kidneys, and liver—was performed to generate volumes of interest (VOIs). Liver metastases were identified using SPECT images with automated gradient-based VOI generation in syngo.via’s RT image suite. The dose volume histogram shows a relatively small portion of the lesion receiving 16.8 Gy, which is evident from the isodose lines and dose volume histogram. The kidneys show low levels of renal cortical absorbed dose as predicted from the quantitative SPECT data, which showed fast washout after initial peak. The mean renal dose was 1.74 Gy for the left kidney and 2.14 Gy for the right kidney. The mean lung dose was also low at approximately 0.1 Gy for both lungs.
In this clinical case example, xSPECT Quant reconstructions from the sequential SPECT/CT data enabled the evaluation of absolute tracer concentration. This enabled a standalone dosimetry software to load the quantitative data and seamlessly co-register the SPECT and CT as well as the SPECT/CT images across multiple timepoints to calculate TACs for every voxel for 3D voxel-based dosimetry.
The resultant images with isodose lines visualized on CT images, as well as dose volume histograms, show high maximum and mean absorbed dose to the liver lesion. The renal and lung dose is low, which ensures the possibility of multiple therapy cycles in this patient. Assuming a cumulative renal absorbed dose threshold of 23 Gy, there is a possibility of more than 6 cycles of therapy in this patient with the assumption that renal dose will remain in the same range for subsequent therapies. This assumption may not apply since tumor shrinkage and decrease in uptake following response to radionuclide therapy may lead to higher levels of tracer clearance and retention in the renal cortex, ultimately leading to a higher absorbed dose in subsequent studies. Thus, sequential SPECT/CT for subsequent therapy cycles is also important for proper management of this patient.
xSPECT Quant enables accurate, reproducible quantification of 177Lu-DOTATATE concentration within lesions and critical organs due to NIST-traceable, source-based system calibration, CT attenuation correction (CTAC), scatter correction, as well as corrections for detector deflection and other variables. Absolute tracer concentration in SPECT datasets using xSPECT Quant can be intrinsically read by third-party dosimetry software without the need for any additional calibration factor for dosimetry calculation. In this patient, the mean absorbed dose to the largest liver lesion (9.4 Gy) is comparable to values obtained from other similar studies. Kairemo et al performed 3D voxel-based dosimetry using sequential SPECT/CT following 7.4 GBq (200 mCi) dose of 177Lu DOTATATE and obtained tumor doses, which varied from 2-10 Gy, while renal dose varied from 3-12 Gy.1
Scanner: Symbia Pro.specta
7.7 GBq (200 mCi) 177Lu DOTATATE
2 bed positions/60 stops per detector, 20 seconds per stop
40 ref mAs
128 x 128 matrix, xSPECTEM 24i4s
32 x 0.7 mm