Total body CD4+ T cell dynamics in treated and untreated SIV infection revealed by in vivo imaging

The peripheral blood represents only a small fraction of the total number of lymphocytes in the body. To develop a more thorough understanding of T cell dynamics, including the effects of SIV/SHIV/HIV infection on immune cell depletion and immune reconstitution following combination antiretroviral therapy (cART), one needs to utilize approaches that allow direct visualization of lymphoid tissues. In the present study, noninvasive in vivo imaging of the CD4+ T cell pool has revealed that the timing of the CD4+ T cell pool reconstitution following initiation of ART in SIV-infected nonhuman primates (NHPs) appears seemingly stochastic among clusters of lymph nodes within the same host. At 4 weeks following initiation or interruption of cART, the changes observed in peripheral blood (PB) are primarily related to changes in the whole-body CD4 pool rather than changes in lymphocyte trafficking. Lymph node CD4 pools in long-term antiretroviral-treated and plasma viral load-suppressed hosts appear suboptimally reconstituted compared with healthy controls, while splenic CD4 pools appear similar between the 2 groups

Theranostic pretargeted radioimmunotherapy of colorectal cancer xenografts in mice using picomolar affinity 86Y- or 177Lu-DOTA-Bn binding scFv C825/GPA33 IgG bispecific immunoconjugates

Purpose: GPA33 is a colorectal cancer (CRC) antigen with unique retention properties after huA33-mediated tumor targeting. We tested a pretargeted radioimmunotherapy (PRIT) approach for CRC using a tetravalent bispecific antibody with dual specificity for GPA33 tumor antigen and DOTA-Bn–(radiolanthanide metal) complex. Methods: PRIT was optimized in vivo by titrating sequential intravenous doses of huA33-C825, the dextran-based clearing agent, and the C825 haptens [superscript 177]Lu-or [superscript 86]Y-DOTA-Bn in mice bearing the SW1222 subcutaneous (s.c.) CRC xenograft model. Results: Using optimized PRIT, therapeutic indices (TIs) for tumor radiation-absorbed dose of 73 (tumor/blood) and 12 (tumor/kidney) were achieved. Estimated absorbed doses (cGy/MBq) to tumor, blood, liver, spleen, and kidney for single-cycle PRIT were 65.8, 0.9 (TI 73), 6.3 (TI 10), 6.6 (TI 10), and 5.3 (TI 12), respectively. Two cycles of PRIT (66.6 or 111 MBq [superscript 177]Lu-DOTA-Bn) were safe and effective, with a complete response of established s.c. tumors (100 – 700 mm³) in nine of nine mice, with two mice alive without recurrence at >140 days. Tumor log kill in this model was estimated to be 2.1 – 3.0 based on time to 500-mm³ tumor recurrence. In addition, PRIT dosimetry/diagnosis was performed by PET imaging of the positron-emitting DOTA hapten [superscript 86]Y-DOTA-Bn. Conclusion: We have developed anti-GPA33 PRIT as a triplestep theranostic strategy for preclinical detection, dosimetry, and safe targeted radiotherapy of established human colorectal mouse xenografts.National Institute of Mental Health (U.S.) (Grant R01-CA-101830

Addressing the disparities in dementia risk, early detection and care in Latino populations: Highlights from the Second Latinos and Alzheimer's Symposium

The Alzheimer's Association hosted the second Latinos & Alzheimer's Symposium in May 2021. Due to the COVID-19 pandemic, the meeting was held online over 2 days, with virtual presentations, discussions, mentoring sessions, and posters. The Latino population in the United States is projected to have the steepest increase in Alzheimer's disease (AD) in the next 40 years, compared to other ethnic groups. Latinos have increased risk for AD and other dementias, limited access to quality care, and are severely underrepresented in AD and dementia research and clinical trials. The symposium highlighted developments in AD research with Latino populations, including advances in AD biomarkers, and novel cognitive assessments for Spanish-speaking populations, as well as the need to effectively recruit and retain Latinos in clinical research, and how best to deliver health-care services and to aid caregivers of Latinos living with AD

Prevotella spp y Porphyromonas spp en adultos jóvenes con enfermedad periodontal

Se ha establecido la relación causal de microorganismos en la enfermedad periodontal prestando interés en la investigación de especies bacterianas anaerobias, para determinar en cada región o país, el perfil epidemiológico asociado a la enfermedad periodontal, en Colombia se han realizado algunos esfuerzos aislados para lograr esto

Discordant localization of 2-[18F]-fluoro-2-deoxy-D-glucose in 6-[18F]-fluorodopamine- and [(123)I]-metaiodobenzylguanidine-negative metastatic pheochromocytoma sites

Although the majority of pheochromocytomas (PHEO) are benign, a subset is malignant. Computed tomography (CT) and magnetic resonance imaging (MRI) localize PHEO with high sensitivity but, because of limited specificity, [(131)I]- or [(123)I]-metaiodobenzylguanidine ([(131)I]- or [(123)I]-MIBG) is often used as a complementary agent. 6-[18F]-fluorodopamine ([18F]-DA) has been developed as a radiopharmaceutical for the targeting of noradrenergic pathways, and has been shown to result in a better detection rate of PHEO sites than MIBG; however, [18F]-DA has shown a lack of accumulation in some patients with metastatic PHEO. Five patients with widespread metastatic PHEO who had CT and MRI evidence of metastatic disease (one man and four women; age range, 25-64 years), and who underwent imaging with [(123)I]-MIBG, [18F]-DA and 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]-FDG), were evaluated retrospectively. Tomographic imaging was performed and positron emission tomography (PET) images were inspected visually and quantitatively. All five patients had [(123)I]-MIBG scans that grossly underestimated the extent of disease when compared with conventional CT and MRI. All lesions seen on [(123)I]-MIBG scans were detected on [18F]-DA scans, which also detected additional lesions. Nonetheless, [18F]-DA also failed to detect numerous lesions seen on CT and MRI. In all of these cases, [18F]-FDG PET showed lesions that were not detected on either [(123)I]-MIBG or [18F]-DA scans. When [(123)I]-MIBG or [18F]-DA fails to localize lesions seen on conventional imaging studies, [18F]-FDG may be recommended as an ancillary test for the diagnosis and localization of metastatic PHEO. This is particularly important in patients with aggressive PHEO

Annotating STEAP1 Regulation in Prostate Cancer with 89Zr Immuno-PET

UnlabelledAntibodies and antibody-drug conjugates targeting the cell surface protein 6 transmembrane epithelial antigen of prostate 1 (STEAP1) are in early clinical development for the treatment of castration-resistant prostate cancer (PCa). In general, antigen expression directly affects the bioactivity of therapeutic antibodies, and the biologic regulation of STEAP1 is unusually complicated in PCa. Paradoxically, STEAP1 can be induced or repressed by the androgen receptor (AR) in different human PCa models, while also expressed in AR-null PCa. Consequently, there is an urgent need to translate diagnostic strategies to establish which regulatory mechanism predominates in patients to situate the appropriate therapy within standard of care therapies inhibiting AR.MethodsTo this end, we prepared and evaluated (89)Zr-labeled MSTP2109A ((89)Zr-2109A), a radiotracer for PET derived from a fully humanized monoclonal antibody to STEAP1 in preclinical PCa models.Results(89)Zr-2109A specifically localized to the STEAP1-positive human PCa models CWR22Pc, 22Rv1, and PC3. Moreover, (89)Zr-2109A sensitively measured treatment-induced changes (∼66% decline) in STEAP1 expression in CWR22PC in vitro and in vivo, a model we showed to express STEAP1 in an AR-dependent manner.ConclusionThese findings highlight the ability of immuno-PET with (89)Zr-2109A to detect acute changes in STEAP1 expression and argue for an expansion of ongoing efforts to image PCa patients with (89)Zr-2109A to maximize the clinical benefit associated with antibodies or antibody-drug conjugates to STEAP1