Performance and long-term consistency of five Galliform 68Ge/68Ga generators used for clinical Ga-68 preparations over a 4 year period.

BACKGROUND: Gallium-68 is a positron emitter for PET applications that can be produced without cyclotron by a germanium (Ge-68) chloride/gallium (Ga-68) chloride generator. Short half-life (67.71 min) of Ga-68, matching pharmacokinetic properties of small biomolecules, facilitates isotope utilization in compounding radiopharmaceuticals for PET imaging. The increasing cost of good manufacturing practice-compliant generators has strengthened the need for radionuclide efficient use by planning specific radiopharmaceutical sessions during the week, careful maintenance of the generator and achievement of high labeling yield and radiochemical purity (RCP) of the radiolabeled molecules. METHODS: The aim of this study was to evaluate the annual performance of five consecutive 68Ge/68Ga generators used for small-scale preparations of 68Ga-radiopharmaceuticals. To assess the long-term efficiency of isotope production we measured the weekly elution yield. To assess process efficiency we measured elution yield, labeling yield and RCP of four radiopharmaceutical preparations (68Ga-DOTATOC, 68Ga-PSMA-HBED-CC, 68Ga-PENTIXAFOR and 68Ga-DOTATATE). RESULTS: The annual mean elution yield of the generators was 74.7%, higher than that indicated by the manufacturer, and it never went below 65%. The Ge-68 level in the final products was under the detection limits in all the produced batches (mean value 0.0000048%). The RCP of radiopharmaceuticals determined by high-performance liquid chromatography was 98 ± 0.22%. The mean yield of radiolabelling was 64.68, 68.71, 57 and 63.68% for 68Ga-DOTATOC, 68Ga-PSMA-HBED-CC, 68GaPENTIXAFOR and 68Ga-DOTATATE. CONCLUSION: The ability to prepare in the hospital radiopharmacy high-purity and pharmaceutically acceptable 68Ga-radiolabeled probes on a routine basis facilitates patient access to precision imaging for clinical and research aims.

Correlation between 18F-FDG PET/CT and diffusion-weighted MRI parameters in head and neck squamous cell carcinoma at baseline and after chemo-radiotherapy. A retrospective single institutional study.

OBJECTIVES: The relationship between glucose metabolism and tumor cellularity before chemo-radiotherapy in patients with head and neck squamous cell carcinoma (SCC) has never been compared with that of patients evaluated after treatment. This retrospective study analyzed the correlation between glucose metabolism parameters expressed by standardized uptake value (SUV) derived from 18F-fluorodeoxyglucose (18F-FDG) PET/CT and cellularity tumor parameters expressed by apparent diffusion coefficients (ADC) derived from diffusion-weighted (DW) MRI in untreated and treated patients with head and neck SCC. METHODS: In 19 patients with no previous exposure to any treatment and 17 different chemo-radiotreated patients with head and neck SCC, we correlated the semi-quantitative uptake values (SUVmax, SUVpeak, and SUVmean) with the ADC functional parameters (ADCmin, ADCmean) including the standard deviation of ADC values (ADCsd). RESULTS: No significant correlation was found between glucose metabolism parameters and ADCmin or ADCmean in untreated and treated patient groups. However, in untreated patients, significant inverse correlations were found between ADCsd and SUVmax (P = 0.039, r = -0.476), SUVpeak (P = 0.003, r = -0.652) and SUVmean (P = 0.039, r = -0.477). Analyses after chemo-radiotherapy in 17 patients showed no significant correlation between glucose metabolism parameters and DW MRI values, excluding a persistent significant (but lower intensity) inverse correlation between SUVpeak and ADCsd (P = 0.033, r = -0.519). CONCLUSIONS: The demonstrated relationships suggest complex interactions especially between metabolic activity and heterogeneity of tumoral tissue, which might play a complementary role in the assessment of head and neck SCC. TRIAL DATE OF REGISTRATION AND REGISTRATION NUMBER: Our retrospective study was registered on April 9th, 2020 by the Ethics Committee of the Coordinating Center "Area Vasta Nord Ovest" (CEAVNO) with Registration Number CEAVNO09042020.

Novel Experience in Hybrid Tracers: Clinical Evaluation of Feasibility and Efficacy in Using ICG-99mTc Nanotop for Sentinel Node Procedure in Breast Cancer Patients.

PURPOSE: The clinical introduction of a radioactive and fluorescent hybrid tracer allowed for preoperative lymphatic mapping and intraoperative real-time fluorescence tracing of the sentinel lymph node (SLN) by a single injection. The aim of this feasibility study is to evaluate the first-in-human use of the hybrid tracer by combining indocyanine green (ICG) and radiocolloid based on Nanotop compound (99mTc Nanotop) for SLN biopsy (SLNB) in breast cancer patients. METHODS: The day before surgery, ICG-99mTc Nanotop was injected periareolarly in breast cancer patients scheduled for SLNB. Planar lymphoscintigraphic (PL) and SPECT/CT images were then acquired. An intraoperative optonuclear probe was used to detect SLN gamma and fluorescent signals. The harvested SLNs were examined by hematoxylin-eosin staining, and patients were clinically evaluated 1 month after surgery. RESULTS: Twenty-one consecutive patients were enrolled. The PL and SPECT/CT techniques identified at least 1 SLN in all patients for a preoperative sentinel detection rate of 100%. SPECT/CT revealed 3 additional lymph nodes in the same nodal basin, which had not been visualized on conventional PL (κ = 0.747; P < 0.005). All 30 preoperative SLNs were localized and excised up to 16 hours after injection. The counts measured via gamma tracing showed a very strong correlation with those measured via near-infrared fluorescent tracing (P < 0.005, r = 0.964). No adverse reactions were observed. CONCLUSIONS: The SLNB technique used with the ICG-99mTc Nanotop tracer resulted to be feasible, reliable, and safe. This hybrid compound allowed us to obtain excellent performance in terms of both preoperative lymphatic mapping and intraoperative SLN detection in breast cancer patients.

Comparison of 99mTc-Labeled Colloid SPECT/CT and Planar Lymphoscintigraphy in Sentinel Lymph Node Detection in Patients with Melanoma: A Meta-Analysis.

We compared the detection rate (DR) for sentinel lymph nodes (SLN), the number of SLNs and the subjects with additional SLNs of single-photon emission computed tomography (SPECT/CT) and planar lymphoscintigraphy (PL) in patients with melanoma. Furthermore, we evaluated the impact of SPECT/CT on surgical plans. Articles containing head-to-head comparisons between SPECT/CT and PL were searched in Pubmed/MEDLINE and Scopus. The literature search was updated until December 31st, 2019. DR was calculated on a per patient-based analysis; the studies were pooled by their odds ratios (ORs) with a random effects model to assess the significance of difference (p < 0.05). The number of additional SLNs (calculated as the relative risk) and pooled proportion of patients with additional SLNs were investigated. The pooled ratio of surgical procedures influenced by the SPECT/CT findings was calculated. Seventeen studies with 1438 patients were eligible for the calculation of DR of SPECT/CT and PL. The average DR was 98.28% (95% confidence interval (95% CI): 97.94-99.19%) for the SPECT/CT and 95.53% (95% CI: 92.55-97.77%) for the PL; OR of 2.31 (95% CI: 1.66-4.18, p < 0.001) in favor of the SPECT/CT. There was a relative risk of a higher number of SLNs (1.13) for the SPECT/CT and 17.87% of patients with additional SLNs were detected by SPECT/CT. The average impact of SPECT/CT on surgery resulted in 37.43% of cases. This meta-analysis favored SPECT/CT over PL for the identification of SLNs in patients with melanoma due to a higher DR, reproducibility, number of SLNs depicted, proportion of patients with additional SLNs and the impact on the surgical plan. However, PL remains a good option due to the high values of the DR for SLNs.

The sentinel lymph node biopsy technique in papillary thyroid carcinoma: The issue of false-negative findings.

BACKGROUND: The management of papillary thyroid carcinoma (PTC) is changed after introduction of sentinel lymph node biopsy (SNB) technique for nodal staging. Some debate still surrounds the accuracy of this procedure in terms of wide heterogeneity of sentinel lymph node detection and false-negative findings. AIM: to identify the key issues which make it difficult the usefulness of SNB in PTC. METHODS: A comprehensive computer literature search of meta-analyses published in PubMed/MEDLINE and Cochrane library database until June 30, 2019 was conducted. We used a search algorithm based on this combination of terms: (i) "thyroid neoplasm" or "thyroid cancer" or "thyroid carcinoma" or "thyroid malignancy" or "meta-analysis" or "systematic review") AND (ii) "sentinel lymph node biopsy". RESULTS: Comparing 4 written meta-analyses published in the literature, the diagnostic performance of SNB technique in PTC has been summarized. Relatively high false-negative rates (FNR) were reported for each SNB methods: vital-dye (VD: 12.7%; 7%; 0-38%), 99mTc-nanocolloid planar lymphoscintigraphy with the use of intraoperative hand-held gamma probes (LS: 11.3%; 16%; 0-40%), combined LS with VD (LS+VD: 0%; 0-17%), LS with the additional contribution of preoperative SPECT/CT (7-8%). CONCLUSION: Evidence-based data about the diagnostic performance of SNB in PTC are increasing. The nuclear medicine community should reach a consensus on the operational definition of the SLN to better guide the surgeon in identifying the lymph nodes most likely contain metastatic cells. Standardization of SLN identification, removal and analysis are required.

Detection of Uterine Leiomyosarcoma Peritoneal Lesions by SPECT/CT and ROLL Technique.

We reported the preoperative radio-guided localization of 4 peritoneal metastatic nodules in the case of a 45-year-old woman with uterine leiomyosarcoma. Three lines of chemotherapy were tried, but cardiotoxicity occurred. Within the context of so-called GOSTT (guided intraoperative scintigraphic tumor targeting), preoperative radio-guided localization of peritoneal metastases enabled their subsequent radio-guided excisional biopsy. SPECT/CT allowed for anatomical localization of the hot lesions and generated a 3-dimensional volume-rendering roadmap, facilitating a surgical approach.

Effect of Sentinel Node Biopsy in Clinically N0, BRAF V600E-Mutated, Small Papillary Thyroid Carcinoma: A Pilot Study.

PURPOSE: BRAF V600E mutation papillary thyroid cancer (PTC) is more aggressive with a higher risk of lymph node involvement and a poorer prognosis. Prior studies failed to demonstrate the superiority of prophylactic lymphadenectomy. We investigated the utility of additional radio-guided sentinel node biopsy (SNB). METHODS: We analyzed 15 patients with N0 PTC by ultrasound and BRAF mutation on preoperative biopsy treated with total thyroidectomy (TT) or TT + prophylactic central neck dissection (PCND) alone or with SNB. Conventional surgery was performed before SNB. We recorded primary tumor diameter, multifocality, extrathyroid infiltration, neoplastic emboli, and tall cell variant. At follow-up, we evaluated basal and stimulated thyroglobulin and ultrasound or radioiodine scintigraphy. RESULTS: Of 15 consecutive patients, 5 received conventional surgery alone, and 10 had SNB. For the first group, 4 underwent TT, and 1 had TT + PCND. Among the SNB group, 1 had no sentinel node detected and underwent a simple TT, 2 had TT + PCND+ SNB in the lateral compartment, and 7 had TT + SNB in 1 to 3 neck compartments. Micrometastases were found in 1 of 3 PCND specimens. Sentinel node biopsy revealed metastasis in 3 of 6 central compartment biopsies, in 2 of 6 biopsies in the ipsilateral lateral compartment, and in none of 2 biopsies in the contralateral compartment. Sentinel node biopsy allowed the removal of micrometastases in 4 of 10 patients. At 53 months' (mean) follow-up, no relapse was documented. CONCLUSIONS: Radio-guided SNB correctly and efficiently stages cN0 BRAF-mutated PTC patients. Sentinel node biopsy could limit time-consuming, risk-exposing compartmental prophylactic dissections.

Sentinel Lymph Node Biopsy in Small Papillary Thyroid Cancer: A Meta-analysis.

PURPOSE: The aim of this study was to compare reported results on available techniques for sentinel lymph node detection rate (SDR) in papillary thyroid cancer (PTC). METHODS: The MEDLINE database was searched via a PubMed interface to identify original articles regarding sentinel lymph node biopsy (SNB) in thyroid cancer. Studies were stratified according to the sentinel lymph node (SLN) detection technique: vital-dye (VD), Tc-nanocolloid planar lymphoscintigraphy with the use of intraoperative hand-held gamma probes (LS), both Tc-nanocolloid planar lymphoscintigraphy with intraoperative use of hand-held gamma probe and VD (LS + VD), Tc-nanocolloid planar lymphoscintigraphy with the additional contribution of preoperative SPECT/CT, and intraoperative use of hand-held gamma probe (LS-SPECT/CT). Pooled SDR values were presented with a 95% confidence interval (CI) for each SLN detection techniques. A Z-test was used to compare pooled SDR estimates. False-negative rates were summarized for each method. RESULTS: Forty-five studies were included. Overall SDRs for the VD, LS, LS + VD, and LS-SPECT/CT techniques were 83% (95% CI, 77%-88%; I = 78%), 96% (95% CI, 90%-98%; I = 68%), 87% (95% CI, 65%-96%; I = 75%), and 93% (95% CI, 86%-97%; I = 0%), respectively. False-negative rates were 0% to 38%, 0% to 40%, 0% to 17%, and 7% to 8%, respectively. CONCLUSIONS: In patients with PTC, Tc-nanocolloids offer a higher SDR than that of the VD technique. The addition of SPECT/CT improved identification of metastatic SLNs outside the central neck compartment.

Extraocular muscle sampled volume in Graves' orbitopathy using 3-T fast spin-echo MRI with iterative decomposition of water and fat sequences.

BACKGROUND: Current magnetic resonance imaging (MRI) techniques for measuring extraocular muscle (EOM) volume enlargement are not ideally suited for routine follow-up of Graves' ophthalmopathy (GO) because the difficulty of segmenting the muscles at the tendon insertion complicates and lengthens the study protocol. PURPOSE: To measure the EOM sampled volume (SV) and assess its correlation with proptosis. MATERIAL AND METHODS: A total of 37 patients with newly diagnosed GO underwent 3-T MRI scanning with iterative decomposition of water and fat (IDEAL) sequences with and without contrast enhancement. In each patient, the three largest contiguous coronal cross-sectional areas (CSA) on the EOM slices were segmented using a polygon selection tool and then summed to compute the EOM-SV. Proptosis was evaluated with the Hertel index (HI). The relationships between the HI value and EOM-SV and between HI and EOM-CSA were compared and assessed with Pearson's correlation coefficient and the univariate regression coefficient. Inter-observer and intra-observer variability were calculated. RESULTS: HI showed a stronger correlation with EOM-SV (P < 0.001; r = 0.712, r2 = 0.507) than with EOM-CSA (P < 0.001; r = 0.645 and r2 = 0.329). The intraclass correlation coefficient indicated that the inter-observer agreement was high (0.998). The standard deviation between repeated measurements was 1.9-5.3%. CONCLUSION: IDEAL sequences allow for the measurement EOM-SV both on non-contrast and contrast-enhanced scans. EOM-SV predicts proptosis more accurately than does EOM-CSA. The measurement of EOM-SV is practical and reproducible. EOM-SV changes of 3.5-8.3% can be assumed to reflect true volume changes.

Sentinel lymph node biopsy in small papillary thyroid cancer. A review on novel surgical techniques.

PURPOSE: Sentinel lymph node biopsy (SNB) in patients with papillary thyroid carcinoma (PTC) and negative for clinically neck lymph node metastatic involvement (N0) has emerged as a promising minimally invasive procedure to detect metastatic nodes. METHODS: The MEDLINE database was searched via the PubMed interface on 10 January 2018 for the MeSH headings "sentinel lymph node biopsy" and "thyroid carcinoma". RESULTS: Vital blue dye, radioisotope, and the combination of both techniques are used in PTC patients. These methods and the emerging role of SPECT/CT are discussed in this review. The sentinel lymph node (SLN) identification rates ranged from 0 to 100% for blue dye, 83 to 100% for radioisotopes, and 66 to 100% for the combination of both techniques, respectively. CONCLUSIONS: SNB based on radioisotope technique with the use of intraoperative gamma-probe is an accurate and safe method that allows the highest SLN detection rate. There is sufficient evidence to propagate the increasing use of SNB procedure that has the potential to avoid prophylactic lymph node surgery in patients clinically N0.