Hot Embolus Artifact Mimicking Disease Progression in Post-therapy ¹⁷⁷Lu-DOTATATE Scan: Incremental Value of SPECT/CT

Abstract

Peptide receptor radionuclide therapy (PRRT) has become an established treatment for patients with inoperable and/or metastatic, well-differentiated neuroendocrine tumors with overexpression of somatostatin receptor type 2 (SSTR-2). The post-therapy ¹⁷⁷Lu-DOTATATE whole-body scan not only assesses the biodistribution of the lesions seen on pre-therapy ⁶⁸ Ga-SSTR PET/CT scan but also provides a quick assessment of disease status and dosimetry during treatment. Like any other radionuclide scan, the whole-body ¹⁷⁷Lu-DOTATATE scan may also show abnormal radiotracer uptake, which may require further imaging to establish its exact etiology. Though radiotracer emboli mimicking focal pulmonary lesions have been described with ¹⁸F-FDG and ⁶⁸ Ga-DOTANOC PET/CT scans, similar artifacts with post-therapy ¹⁷⁷Lu-DOTATATE scans have not been described. Herein, we report two cases of hot emboli in the post-therapy ¹⁷⁷Lu-DOTATATE scans.

Introduction

Artifacts on single positron emission computed tomography (SPECT) and positron emission tomography (PET) imaging are common occurrences. However, artifacts due to radiotracer embolus are rare and can have a significant impact on the further course and disease management if not evaluated carefully. Though radiotracer emboli mimicking focal pulmonary lesions have been described with ¹⁸F-fluorodeoxyglucose (FDG) and ⁶⁸ Ga-DOTANOC PET/CT scans, similar artifacts observed in post-therapy ¹⁷⁷Lu-DOTATATE scans have not been described yet. We report two cases of radiotracer emboli in the post-therapy ¹⁷⁷Lu-DOTATATE scans mimicking new disease sites.

Case Report

A 35-year-old woman with histopathologically proven metastatic grade 2 neuroendocrine tumor (NET) of the stomach, was planned for peptide receptor radionuclide therapy (PRRT) (200 mCi of ¹⁷⁷Lu-DOTATATE/cycle) at 8-week intervals along with amino acid nephroprotection after detailed work-up. After two cycles of ¹⁷⁷Lu-DOTATATE, the patient underwent an interim ⁶⁸ Ga-DOTANOC PET/CT scan for response assessment. Her maximum intensity projection (MIP) image (Fig. 1a) showed somatostatin receptor (SSTR) expressing lesions in the stomach and liver. The patient received 2 more cycles of ¹⁷⁷Lu-DOTATATE at 8-week intervals. After the 4th cycle of ¹⁷⁷Lu-DOTATATE, the whole-body post-therapy scan acquired at 24 h showed a new focus of increased radiotracer uptake in the left thoracic region (Fig. 1b, c, arrows). SPECT/CT done for lesion localization and characterization revealed an abnormal focus of increased radiotracer activity in the lower lobe of the left lung parenchyma without any corresponding anatomical lesion on axial CT (Fig. 1d, e). Follow-up ⁶⁸ Ga-DOTANOC PET/CT (Fig. 1f) acquired 2 months after the 4th cycle of ¹⁷⁷Lu-DOTATATE did not reveal any focus of radiotracer activity in the left thoracic region, confirming the previously noted uptake to be an artifact.

Fig. 1.

a Interim ⁶⁸ Ga-DOTANOC PET maximum intensity projection (MIP) image showing somatostatin expressing lesions in the upper abdominal region. Anterior (b) and posterior (c) whole-body ¹⁷⁷Lu-DOTATATE scans post the 4th cycle (radiotracer 200 mCi) showing focal radiotracer uptake in the left thoracic region (arrows). Axial sections of fused SPECT/CT (d) of the thorax revealed focal radiotracer localization in the left lung parenchyma without any anatomical lesion on corresponding CT images (e). Follow-up ⁶⁸ Ga-DOTANOC PET MIP image (f) showing no abnormal focus of radiotracer uptake in the thoracic region

Another 43-year-old woman, with biopsy-proven metastatic grade 2 NET (Ki 67 index 15%) was evaluated for PRRT. MIP image (Fig. 2a) of ⁶⁸ Ga-DOTANOC PET/CT scan revealed SSTR-expressing lesions in the bowel loops, regional lymph nodes, pancreas, liver, peritoneum, omentum, and serosa. In addition to these radiotracer avid lesions, her planar whole-body scan acquired 24 h after therapy with radiotracer 200 mCi of ¹⁷⁷Lu-DOTATATE (1st cycle), revealed an abnormal focus of increased radiotracer activity (Fig. 2b, c, arrows) in the right upper thoracic region. Fused SPECT/CT images of the thorax localized the focus of abnormal radiotracer activity to the apical right lung parenchyma without any corresponding lesion on axial CT images (Fig. 2d, e). Follow-up post-therapy imaging after 2nd cycle of ¹⁷⁷Lu-DOTATATE (Fig. 2f, g) did not show any abnormal radiotracer uptake in the right thorax, confirming the previously noted uptake to be artifactual due to radiotracer embolus.

Fig. 2.

a Pre-therapy ⁶⁸ Ga-DOTANOC PET maximum intensity projection (MIP) image showing multiple somatostatin-expressing lesions in the abdominopelvic region. Anterior (b) and posterior (c) whole-body ¹⁷⁷Lu-DOTATATE post-therapy scans after the 1st cycle (radiotracer 200 mCi) showing focal radiotracer uptake in the right upper thoracic region (arrows). Axial sections of fused SPECT/CT (d) of the thorax revealed focal radiotracer localization in the right lung parenchyma without any anatomical lesion on corresponding CT images (e). Follow-up anterior (f) and posterior (g) whole-body ¹⁷⁷Lu-DOTATATE scans after 2nd cycle showed no abnormal focus of radiotracer uptake in the thoracic region

Discussion

Few case reports and case series have described the finding of focal ¹⁸F-FDG activity in the lung without an anatomical correlate on corresponding CT images as artifactual. It has been given different names like “hot clot” or “hot embolus” artifact [1–6]. Similar findings have also been described for ⁶⁸ Ga-DOTANOC PET/CT [7, 8]. Even though the incidence of this artifact is very low, it may lead to a false-positive diagnosis of primary malignant or metastatic disease, especially without a careful analysis of hybrid imaging. One of the postulated mechanisms is ¹⁸F-FDG avid infection or inflammation that precedes structural findings. Overexpression of somatostatin receptor type 2 on macrophages recruited in pulmonary infection/inflammation can also cause ⁶⁸ Ga-DOTANOC uptake [7]. However, this possibility was also ruled out due to the negative concurrent CT images along with subsequent negative imaging. Faulty injection technique has been attributed to hot pulmonary microembolus formation secondary to agglutination of radiopharmaceutical by concentrated erythrocytes/platelets during the process of injection; however, exact mechanism is still not clear [2, 9]. To the best of our knowledge, this is the first occurrence of such hot embolus artifacts on ¹⁷⁷Lu-DOTATATE post-therapy whole-body scan. Both patients underwent therapy on the same day, and the radiopharmaceutical was administered using an infusion pump through an intravenous cannula. Another two patients receiving ¹⁷⁷Lu-DOTATATE therapy on the same day did not show any artifacts in their post-therapy imaging. Adequate radiochemical purity (> 95%) was ensured before infusion. Probable reasons for such an artifact could either be due to a fault in the different infusion pump components or a faulty intravenous cannulation technique.

These case reports emphasize the importance of careful scrutiny of ¹⁷⁷Lu-DOTATATE post-therapy scan using additional imaging techniques like SPECT/CT to differentiate artifactual findings from actual lesions to avoid misinterpretation and change in the treatment plans.

Author Contribution

Piyush Aggarwal participated in the drafting of the manuscript, data acquisition, and data analysis. Anupriya Anwariya participated in the drafting of the manuscript and data acquisition. Anwin Joseph Kavanal participated in the data acquisition, data analysis, study conception, and manuscript revision. Santosh Ranjan Jena participated in the data acquisition and data analysis. Ashwani Sood participated in the study conception and design, data analysis, manuscript revision, and approval of the final content of the manuscript. Bhagwant Rai Mittal participated in the manuscript revision and approval of the final content of the manuscript. All the authors read and approved the final manuscript.

Data Availability

Data sharing is not applicable to this article, as no data sets were generated or analyzed during the current study.

Declarations

Ethical Approval and Consent to Participate

The present study was approved by the institutional review board of our institution (IRB number: NK/6191/Res/206) and with the 2013 Helsinki declaration and its later amendments or comparable ethical standards.

Consent for Publication

The institutional review board at our institution approved this retrospective study, and the requirement to obtain informed consent was waived.

Conflict of Interest

Conflict of Interest Piyush Aggarwal, Anupriya Anwariya, Anwin Joseph Kavanal, and Ashwani Sood, Santosh Ranjan Jena, and Bhagwant Rai Mittal declare no conflict of interest.