Comparison of [99mTc]Tc-tilmanocept with [99mTc]Tc-sulphur colloids and [99mTc]Tc-albumin colloids for sentinel lymph node detection in patients with cutaneous malignancies of the head.

PURPOSE: Sentinel lymph node (SLN) biopsy is a staging procedure in the management of cutaneous malignancies of the head. The ideal radiopharmaceutical is controversial. This study aimed to compare [99mTc]Tc-tilmanocept (TcTM) with [99mTc]Tc-sulphur colloid (TcSC) and [99mTc]Tc-albumin colloid (TcAC) for SLN detection in the head and neck region. METHODS: Data from 62 patients with cutaneous malignancies of the head who were injected with TcTM, TcSC, or TcAC before SLN imaging (SLN-I) and SLN excision (SLN-E) between 2012 and 2021 were retrospectively analysed. SLN-I was performed using planar lymphoscintigraphy and SPECT/CT, and a gamma probe was used for SLN-E. The SLN-I localisation rate (patients with SLNs) and degree (SLN number) and SLN-E relocalisation rate (patients with SLNs) and ratio (SLN number in SLN-E/SLN number in SLN-I) were compared between TcTM, TcSC, and TcAC. RESULTS: TcTM showed similar SLN-I localisation rates for primaries in the anterior and posterior head region compared with TcSC (84.6% vs. 72.4%, p=0.680; both 100.0%) and TcAC (84.6% vs. 75.0%, p=1.000; both 100.0%). The SLN-I localisation degree for TcTM was higher for primaries in the anterior head region and similar for primaries in the posterior head region compared with TcSC (3.2 vs. 2.3, p=0.034; and 1.8 vs. 2.2, p=0.506) and TcAC (3.2 vs. 2.0, p=0.038; and 1.8 vs. 2.7, p=0.329). The SLN-E relocalisation rates and ratios were similar for all. CONCLUSION: On the basis of a limited study design that compared three different tracers in three different patient groups, TcTM showed comparable overall performance to TcSC and TcAC.

Assessment of Chemotherapy-Induced Organ Damage with Ga-68 Labeled Duramycin.

PURPOSE: Evaluation of [68Ga]NODAGA-duramycin as a positron emission tomography (PET) tracer of cell death for whole-body detection of chemotherapy-induced organ toxicity. PROCEDURES: Tracer specificity of Ga-68 labeled NODAGA-duramycin was determined in vitro using competitive binding experiments. Organ uptake was analyzed in untreated and doxorubicin, busulfan, and cisplatin-treated mice 2 h after intravenous injection of [68Ga]NODAGA-duramycin. In vivo data were validated by immunohistology and blood parameters. RESULTS: In vitro experiments confirmed specific binding of [68Ga]NODAGA-duramycin. Organ toxicities were detected successfully using [68Ga]NODAGA-duramycin PET/X-ray computed tomography (CT) and confirmed by immunohistochemistry and blood parameter analysis. Organ toxicities in livers and kidneys showed similar trends in PET/CT and immunohistology. Busulfan and cisplatin-related organ toxicities in heart, liver, and lungs were detected earlier by PET/CT than by blood parameters and immunohistology. CONCLUSION: [68Ga]NODAGA-duramycin PET/CT was successfully applied to non-invasively detect chemotherapy-induced organ toxicity with high sensitivity in mice. It, therefore, represents a promising alternative to standard toxicological analyses with a high translational potential.

Dual addressing of thymidine synthesis pathways for effective targeting of proliferating melanoma.

Here, we examined the potential of blocking the thymidine de novo synthesis pathways for sensitizing melanoma cells to the nucleoside salvage pathway targeting endogenous DNA irradiation. Expression of key nucleotide synthesis and proliferation enzymes thymidylate synthase (TS) and thymidine kinase 1 (TK1) was evaluated in differentiated (MITFhigh [microphthalmia-associated transcription factor] IGR1) and invasive (MITFmedium IGR37) melanoma cells. For inhibition of de novo pathways cells were incubated either with an irreversible TS inhibitor 5-fluoro-2'-deoxyuridine (FdUrd) or with a competitive dihydrofolate-reductase (DHFR) inhibitor methotrexate (MTX). Salvage pathway was addressed by irradiation-emitting thymidine analog [123/125 I]-5-iodo-4'-thio-2'-deoxyuridine (123/125 I-ITdU). The in vivo targeting efficiency was visualized by single-photon emission computed tomography. Pretreatment with FdUrd strongly increased the cellular uptake and the DNA incorporation of 125 I-ITdU into the mitotically active IGR37 cells. This effect was less pronounced in the differentiated IGR1 cells. In vivo, inhibition of TS led to a high and preferential accumulation of 123 I-ITdU in tumor tissue. This preclinical study presents profound rationale for development of therapeutic approach by highly efficient and selective radioactive targeting one of the crucial salvage pathways in melanomas.

MRI for attenuation correction in PET: methods and challenges.

In current combined PET/MR systems, PET attenuation correction is based on MRI, since the small bore inside MRI systems and the strong magnetic field do not permit a rotating PET transmission source or a CT device to be integrated. Unlike CT measurements in PET/CT scanners, the MR signal is not directly correlated to tissue density and thus cannot be converted by a simple transformation of intensity values. Various approaches have been developed based on templates, atlas information, direct segmentation of T1-weighted MR images, or segmentation of images from special MR sequences. The advantages and disadvantages of these approaches as well as additional challenges will be discussed in this review.

Hybrid spline-based multimodal registration using local measures for joint entropy and mutual information.

We introduce a new hybrid approach for spline-based elastic registration of multimodal medical images. The approach uses point landmarks as well as intensity information based on local analytic measures for joint entropy and mutual information. The information-theoretic similarity measures are computationally efficient and can be optimized independently for each voxel. We have applied our approach to synthetic images, brain phantom images, as well as clinically relevant multimodal medical images. We also compared our measures with previous measures.

Strain rate analysis allows detection of differences in diastolic function between viable and nonviable myocardial segments.

Analysis of diastolic function for assessment of myocardial viability has not been evaluated. Strain rate (SR) analysis allows quantitative segmental analysis of myocardial function and has been used during dobutamine stimulation for assessment of systolic functional reserve. In 37 patients with ischemic left ventricular dysfunction diastolic function was evaluated at rest and during low-dose dobutamine stimulation (10 mug/kg/min) using SR imaging and related to F18-fluorodeoxyglucose positron emission tomography. Analysis of peak early (E waves) and late (A waves) diastolic myocardial SR was performed using apical views. In all, 317 segments had normal function at rest by 2-dimensional echocardiography. A total of 192 segments with dyssynergy at rest were classified by positron emission tomography as viable in 94 cases and nonviable in 98 cases. Dys-synergic segments had lower E and A waves SR compared with normal contracting segments. There were no significant differences in peak E and A waves SR at rest between dys-synergic viable and nonviable segments. With dobutamine stimulation peak E waves SR increased significantly for viable segments (0.89 +/- 0.51-1.06 +/- 0.51 L/s, P < .01) whereas it was unchanged for nonviable segments (0.77 +/- 0.49-0.78 +/- 0.48 L/s, P = .835). Peak A waves SR increased for viable (0.71 +/- 0.55-1.00 +/- 0.56 L/s, P < .01) and nonviable (0.57 +/- 0.47-0.71 +/- 0.58 L/s, P = .023) segments. However, during dobutamine stimulation peak A waves SR was larger ( P < .001) for viable than for nonviable segments. In conclusion, normal contracting segments at rest have higher E and A waves SR compared with dys-synergic segments. Dys-synergic viable myocardial segments demonstrate an increase in E and A waves SR with dobutamine stimulation whereas nonviable segments are less responsive to dobutamine.

Strain rate measurement by doppler echocardiography allows improved assessment of myocardial viability inpatients with depressed left ventricular function.

OBJECTIVES: This study sought to evaluate whether objective assessment of the myocardial functional reserve, using strain rate imaging (SRI), allows accurate detection of viable myocardium. BACKGROUND: Strain rate imaging is a new echocardiographic modality that allows quantitative assessment of segmental myocardial contractility. METHODS: In 37 patients (age 58 +/- 9 years) with ischemic left ventricular dysfunction, myocardial viability was assessed using low-dose (10 microg/kg body weight per min) two-dimensional dobutamine stress echocardiography (DSE), tissue Doppler imaging, SRI and (18)F-fluorodeoxyglucose ((18)FDG) positron emission tomography (PET). The peak systolic tissue Doppler velocity and peak systolic myocardial strain rate were determined at baseline and during low-dose dobutamine stress from the apical views. RESULTS: A total of 192 segments with dyssynergy at rest were classified by (18)FDG PET as viable in 94 and nonviable in 98. An increase of peak systolic strain rate from rest to dobutamine stimulation by more than -0.23 1/s allowed accurate discrimination of viable from nonviable myocardium, as determined by (18)FDG PET with a sensitivity of 83% and a specificity of 84%. Receiver operating characteristic (ROC) curve analysis showed an area under the curve for prediction of nonviable myocardium, as determined by (18)FDG PET using SRI, of 0.89 (95% confidence interval [CI] 0.88 to 0.90), whereas the area under the ROC curve using tissue Doppler imaging was 0.63 (95% CI 0.61 to 0.65). CONCLUSIONS: The increase in the peak systolic strain rate during low-dose dobutamine stimulation allows accurate discrimination between different myocardial viability states. Strain rate imaging is superior to two-dimensional DSE and tissue Doppler imaging for the assessment of myocardial viability.