microSPECT Images Research Articles

Transimmunization for immunotherapy of head and neck squamous cell carcinoma (HNSCC)

Objective. To establish proof of principle of transimmunization (T.I.) in an animal model prior to use in a dendritic cell (DC)-based immunotherapy clinical trial for HNSCC. Methods. Pooled blood from syngeneic Fischer 344 rats was photoactivated in the presence of 8-methoxypsoralen and Ultraviolet-A, followed by overnight incubation to facilitate conversion of monocyte precursors to DC. Cells were matured using pathogen associated molecular patterns (PAMPs) – LPS, CpG DNA, flagellin and Poly I: C. Cells were either labeled with Indium-111 and injected peritumorally followed by in vivo tracking using micro-Single Photon Emission CT (micro-SPECT), or used unlabeled in randomized double-blinded vaccination studies in tumor-bearing animals. Treatment groups included: T.I. cells ± PAMPs, T.I. cells + lysate ± PAMPs and T.I. cells + tumor lysate (TL) containing-NP ± PAMPs. Outcome measures included: mean tumor size, survival and ELISA to study differences in production of IFN-γ and IL-10. Results. There were statistically significant differences in mean tumor size at 2 weeks post-injections (P = 0.033) and overall survival (P = 0.009) in the group treated with T.I. cells alone. Addition of PAMPs made no significant impact on outcome measures. Micro-SPECT images indicated that T.I. cells remain at the site of injection between 24 and 96 h. Conclusions. (1) Immature T.I. cells on their own appear to be significantly more effective than those loaded with antigen, or mature ones. (2) T.I. cells remain at the site of injection for at least 24 h prior to migration to regional lymph nodal area for classical antigen cross-presentation.

Alcohol consumption, mild cognitive impairment, and progression to dementia

To estimate the impact of alcohol consumption on the incidence of mild cognitive impairment and its progression to dementia. We evaluated the incidence of mild cognitive impairment in 1,445 non-cognitively impaired individuals and its progression to dementia in 121 patients with mild cognitive impairment, aged 65 to 84 years, participating in the Italian Longitudinal Study on Aging, with a 3.5-year follow-up. The level of alcohol consumption was ascertained in the year before the survey. Dementia and mild cognitive impairment were classified using current clinical criteria. Patients with mild cognitive impairment who were moderate drinkers, i.e., those who consumed less than 1 drink/day (approximately 15 g of alcohol), had a lower rate of progression to dementia than abstainers (hazard ratio [HR] 0.15; 95% CI 0.03 to 0.78). Furthermore, moderate drinkers with mild cognitive impairment who consumed less than 1 drink/day of wine showed a significantly lower rate of progression to dementia than abstainers (HR 0.15; 95% CI 0.03 to 0.77). Finally, there was no significant association between higher levels of drinking (> or =1 drink/day) and rate of progression to dementia in patients with mild cognitive impairment vs abstainers. No significant associations were found between any levels of drinking and the incidence of mild cognitive impairment in non-cognitively impaired individuals vs abstainers. In patients with mild cognitive impairment, up to 1 drink/day of alcohol or wine may decrease the rate of progression to dementia.

Potential use of drug carried-liposomes for cancer therapy via direct intratumoral injection

Liposomes have recognized advantages as nano-particle drug carriers for tumor therapy. In this study, the pharmacokinetics and distribution of intratumorally administered liposomes were investigated as drug carriers for treating solid tumors via direct intratumoral administration. 99mTc-liposomes were administered intratumorally to nude rats bearing human head and neck squamous cell carcinoma xenografts. Planar gamma camera images were analyzed to evaluate the local retention of the intratumorally administered liposomes. Co-registered pinhole micro-single photon emission computed tomography (SPECT)/computed tomography (CT) images were acquired of the whole animal as well as the dissected tumors to determine intratumoral distribution of the 99mTc-liposomes. For 99mTc-liposomes, there was an initial retention of 47.4 ± 11.0% ( n = 4) in tumors and surrounding tissues. At 20 h, 39.2 ± 10.6% ( n = 4) of 99mTc-activity still remained in the tumor. In contrast, only 18.7 ± 3.3% ( n = 3) of the intratumoral 99mTc-activity remained for unencapsulated 99mTc-complex at 20 h. Pinhole micro-SPECT images demonstrated that 99mTc-liposomes also have a superior intratumoral 99mTc-activity diffusion compared with unencapsulated 99mTc-complex. Higher intratumoral retention of 99mTc-liposomes accompanied by an improved intratumoral diffusion suggests that intratumorally administered liposomal drugs are potentially promising agents for solid tumor local therapy.