Radiolabeled somatostatin analogs represent valuable tools for both in vivo diagnosis and therapy of neuroendocrine tumors (NETs) because of the frequent tumoral overexpression of somatostatin receptors (sst). The 2 compounds most often used in functional imaging with PET are 68 Ga-DOTATATE and 68 Ga-DOTATOC. Both ligands share a quite similar sst binding profile. However, the in vitro affinity of 68 Ga-DOTATATE in binding the sst subtype 2 (sst2) is approximately 10-fold higher than that of 68 Ga-DOTATOC. This difference may affect their efficiency in the detection of NET lesions because it is the sst2 that is predominantly overexpressed in NET. We thus compared the diagnostic value of PET/CT with both radiolabeled somatostatin analogs ( 68 Ga-DOTATATE and 68 Ga-DOTATOC) in the same NET patients. Methods: Forty patients with metastatic NETs underwent 68 Ga-DOTATOC and 68 Ga-DOTATATE PET/CT as part of the work-up before prospective peptide receptor radionuclide therapy. The performance of both imaging methods was analyzed and compared for the detection of individual lesions per patient and for 8 defined body regions. A region was regarded positive if at least 1 lesion was detected in that region. In addition, radiopeptide uptake in terms of the maximal standardized uptake value (SUVmax) was compared for concordant lesions and renal parenchyma. Results: Seventy-eight regions were found positive with 68 Ga-DOTATATE versus 79 regions with 68 Ga-DOTATOC (not significant). Overall, however, significantly fewer lesions were detected with 68 Ga-DOTATATE than with 68 Ga-DOTATOC (254 vs. 262, P , 0.05). Mean 68 Ga-DOTATATE SUVmax across all lesions was significantly lower than 68 P , 0.01). Mean SUVmax for renal parenchyma was not significantly different between 68 Ga-DOTATATE and 68 Ga-DOTATOC (12.7 6 3.0 vs. 13.2 6 3.3). Conclusion: 68 Ga-DOTATOC and 68 Ga-DOTATATE possess a comparable diagnostic accuracy for the detection of NET lesions, with 68 Ga-DOTATOC having a potential advantage. The approximately 10-fold higher affinity for the sst2 of 68 Ga-DOTATATE does not prove to be clinically relevant. Quite unexpectedly, SUVmax of 68 Ga-DOTATOC scans tended to be higher than their 68 Ga-DOTATATE counterparts.
Somatostatin receptor (SSTR) imaging is widely used for guiding the management of neuroendocrine tumor (NET) patients. Ga-DOTATATE approval by the U.S. Food and Drug Administration has triggered widespread clinical interest in SSTR PET/CT throughout the United States. Here, we performed a systematic review and meta-analysis to evaluate the impact of SSTR PET/CT on the management of patients with NETs. A comprehensive literature search was performed using The National Center for Biotechnology Information PubMed online database, applying the following key words: "management" AND "PET" AND "neuroendocrine". Fourteen of 190 studies were deemed suitable based on the following inclusion criteria: original research, cohort study, number of patients 10 or more, and reported change in management after SSTR PET/CT. Change in management across studies was determined by a random-effects model. A total of 1,561 patients were included. Overall, change in management occurred in 44% (range, 16%-71%) of NET patients after SSTR PET/CT. In 4 of 14 studies, SSTR PET/CT was performed after anIn-Octreotide scan. In this subgroup, additional information by SSTR PET/CT led to a change in management in 39% (range, 16%-71%) of patients. Seven of 14 studies differentiated between inter- and intramodality changes, with most changes being intermodality (77%; intramodality, 23%). The management was changed in more than one third of patients undergoing SSTR PET/CT even when performed after anIn-Octreotide scan. Intermodality changes were 3 times more likely than intramodality changes, underlining the clinical impact of SSTR PET/CT.
(18)F-FDG PET/CT resulted in a change of therapeutic procedure in 11 of 90 patients and in a change of patient management through additional diagnostic measures in 8 of 90 patients, and is consequently very helpful in initial staging. At our hospital, (18)F-FDG PET/CT in high-risk patients with differentiated thyroid carcinoma has been established as an initial staging modality.
Thyroid nodules are a common finding, especially in iodine-deficient regions. Ultrasonographic scoring systems such as Thyroid Imaging Reporting And Data System (TIRADS) are helpful in differentiating between benign and malignant thyroid nodules by offering a risk stratification model. Depending on the constellation or number of suspicious ultrasound features, a fine needle biopsy (FNB) is recommended. However, none of the previously published TIRADS considered the functional status of the nodules. Hyperfunctioning thyroid nodules (HTN) were presumed to exclude malignancy with a very high negative predictive value. Particularly in regions where the iodine supply is lower, the majority of HTN are seen in patients with normal TSH levels. Therefore, thyroid scintigraphy is essential for the detection of HTN. We investigated whether TIRADS identifies HTN as non-suspicious. We evaluated 615 HTN (23.2±10.0 mm at maximum diameter in 582 patients ( = 442 female, 57.7±13.2 years, and = 140 male, 60.1 ±12.7 years) detected byTc Pertechnetate or Iodine scintigraphy. Prior to evaluating the scintigraphic appearance, all nodules were analyzed prospectively with sonography, using the TIRADS model referenced in Kwak et al., wherein fine needle biopsy is recommended for TIRADS 4A or higher. We also investigated two subgroups, 42 nodules with available histology as well as 117 patients with subclinical or overt hyperthyroidism. Whereas 15.9% of the nodules were classified as TIRADS 3 or lower and <0.1% as TIRADS 5, most of the nodules were classified as TIRADS 4A (29.3%), 4B (29.3%), and 4C (24.9%), respectively. Altogether, more than 80% of the autonomous thyroid nodules were classified as TIRADS 4A or higher which would result in a recommendation of fine needle biopsy. Focusing on those 117 HTN that were already associated with hyperthyroid laboratory values, the rates were similar: 81.2% were categorized as TIRADS 4A or higher (4A: 33.3%, 4B: 29.9%, 4C:17.1%, 5: 0.9%). In the subgroup of patients who underwent thyroid surgery, all nodules were benign, confirming the known NPV of HTN with regard to malignancy exclusion. Integration of thyroid scintigraphy into the TIRADS model is essential to prevent unnecessary FNB and thyroid surgery.
Iodine-positive bone metastases (BMs) are often resistant after initial radioiodine therapy applying the standard-activity approach. A comprehensive lesion-based response study for BMs has not, to our knowledge, yet been performed. In this study, pretherapy and follow-up 124 I PET/CT data on BMs from differentiated thyroid cancer patients were retrospectively analyzed to assess the relationship between absorbed dose (AD) of radiation and response after initial radioiodine treatment. Methods: Before and after initial radioiodine therapy, patients underwent serial PET/CT scanning after administration of 20-40 MBq of 124 I. The pretherapy PET data were used to segment BM volumes and to predict the average ADs after administration of dosimetry-guided 131 I activity. The lower volume limit of determinability of the applied segmentation method was a sphere volume of 0.16 mL. This volume limit classified the BMs into known-volume and fixed-volume groups with their respective average and minimum ADs. Follow-up 124 I and 18 F-FDG PET/ CT data after treatment were analyzed to assess lesion-based therapy response. Response rates at different AD thresholds were calculated and were expressed as the percentage of completely responding BMs above the respective AD threshold. BMs with a maximum extent greater than twice the PET spatial resolution were visually scored for nonuniformity. Results: In total, 61 BMs in 10 patients were included, of which 46 and 15 comprised the known-volume group and the fixed-volume group, respectively. The median follow-up time was 5.6 mo (range, 3.7-23.2 mo). The median average and median minimum ADs in therapy were 183 Gy (range, 39-3,600 Gy) and 270 Gy (range, 63-1,300 Gy), respectively. A range of response rate of 70%-80% was achieved at an AD threshold range of 350-650 Gy. There were 26 BMs that were amenable to visual assessment of nonuniformity, of which two thirds (17/26) were scored as clearly nonuniform, and the majority (11/17) of these nonuniform BMs responded incompletely. Conclusion: Both the high AD threshold associated with high response rates and the low median AD per unit of 131 I activity elucidate the difficulty in achieving therapeutic efficacy for BMs when a single standard activity is administered. The relatively high AD threshold range is possibly a result of distinct levels of spatial nonuniformity in ADs.
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