Introduction: Development of non-invasive molecular imaging techniques that are based on cellular changes in inflammation has been of active interest for arthritis diagnosis. This technology will allow real-time detection of tissue damage and facilitate earlier treatment of the disease, thus representing an improvement over X-rays, which detect bone damage at the advanced stage. Tracing apoptosis, an event occurring in inflammation, has been a strategy used. PSVue 794 is a low-molecular-weight, near-infrared (NIR)-emitting complex of bis(zinc²⁺-dipicolylamine) (Zn-DPA) that binds to phosphatidylserine (PS), a plasma membrane anionic phospholipid that becomes flipped externally upon cell death by apoptosis. In this study, we evaluated the capacity of PSVue 794 to act as an in vivo probe for non-invasive molecular imaging assessment of rheumatoid arthritis (RA) via metabolic function in murine collagen-induced arthritis, a widely adopted animal model for RA. Methods: Male DBA/1 strain mice were treated twice with chicken collagen type II in Freund’s adjuvant. Their arthritis development was determined by measuring footpad thickness and confirmed with X-ray analysis and histology. In vivo imaging was performed with the NIR dye and the LI-COR Odyssey Image System. The level of emission was compared among mice with different disease severity, non-arthritic mice and arthritic mice injected with a control dye without the Zn-DPA targeting moiety. Results: Fluorescent emission correlated reliably with the degree of footpad swelling and the manifestation of arthritis. Ex vivo examination showed emission was from the joint. Specificity of binding was confirmed by the lack of emission when arthritic mice were given the control dye. Furthermore, the PS-binding protein annexin V displaced the NIR dye from binding, and the difference in emission was numerically measurable on a scale. Conclusions: This report introduces an economical alternative method for assessing arthritis non-invasively in murine models. Inflammation in feet and ankles can be measured longitudinally using the PSVue 794 probe for cell death and with a commonly available multipurpose imager. This technique provides metabolic and functional information that anatomical measurement of footpad swelling or visual determination of arthritic index cannot. It also may decrease the number of animals required per experiment because tissue damage will not necessarily require evaluation by harvesting joints for histology.

Glioblastoma multiforme (GBM), a common type of brain cancer, has a very poor prognosis. In general, viable GBM cells exhibit elevated phosphatidylserine (PS) on their membrane surface compared to healthy cells. We have developed a drug, saposin C-dioleoylphosphatidylserine (SapC-DOPS), that selectively targets cancer cells by honing in on this surface PS. To examine whether SapC-DOPS, a stable, blood–brain barrier-penetrable nanovesicle, could be an effective delivery system for precise targeted therapy of radiation, we iodinated several carbocyanine-based fluorescent reporters with either stable iodine (¹²⁷I) or radioactive isotopes (¹²⁵I and ¹³¹I). While all of the compounds, when incorporated into the SapC-DOPS delivery system, were taken up by human GBM cell lines, we chose the two that best accumulated in the cells (DiI (22,3) and DiD (16,16)). Pharmacokinetics were conducted with ¹²⁵I-labeled compounds and indicated that DiI (22,3)-SapC-DOPS had a time to peak in the blood of 0.66 h and an elimination half-life of 8.4 h. These values were 4 h and 11.5 h, respectively, for DiD (16,16)-SapC-DOPS. Adult nude mice with GBM cells implanted in their brains were treated with ¹³¹I-DID (16,16)-SapC-DOPS. Mice receiving the radionuclide survived nearly 50% longer than the control groups. These data suggest a potential novel, personalized treatment for a devastating brain disease.

Glioblastoma multiforme (GBM), the most common type of brain cancer, is extremely aggressive and has a dreadful prognosis. GBM comprises 60% of adult brain tumors and the 5 year survival rate of GBM patients is only 4.3%. Standard-of-care treatment includes maximal surgical removal of the tumor in combination with radiation and temozolomide (TMZ) chemotherapy. TMZ is the “gold-standard” chemotherapy for patients suffering from GBM. However, the median survival is only about 12 to 18 months with this protocol. Consequently, there is a critical need to develop new therapeutic options for treatment of GBM. Nanomaterials have unique properties as multifunctional platforms for brain tumor therapy and diagnosis. As one of the nanomaterials, lipid-based nanocarriers are capable of delivering chemotherapeutics and imaging agents to tumor sites by enhancing the permeability of the compound through the blood–brain barrier, which makes them ideal for GBM therapy and imaging. Nanocarriers also can be used for delivery of radiosensitizers to the tumor to enhance the efficacy of the radiation therapy. Previously, high-atomic-number element-containing particles such as gold nanoparticles and liposomes have been used as radiosensitizers. SapC–DOPS, a protein-based liposomal drug comprising the lipid, dioleoylphosphatidylserine (DOPS), and the protein, saposin C (SapC), has been shown to be effective for treatment of a variety of cancers in small animals, including GBM. SapC–DOPS also has the unique ability to be used as a carrier for delivery of radiotheranostic agents for nuclear imaging and radiotherapeutic purposes. These unique properties make tumor-targeting proteo-liposome nanocarriers novel therapeutic and diagnostic alternatives to traditional chemotherapeutics and imaging agents. This article reviews various treatment modalities including nanolipid-based delivery and therapeutic systems used in preclinical and clinical trial settings for GBM treatment and detection.

Purpose Previous studies indicate that ^99mTc- and fluorescent-labeled c[Cys-Thr-Pro-Ser-Pro-Phe-Ser-His-Cys]OH (TCP-1) peptides were able to detect colorectal cancer (CRC) and tumor-associated vasculature. This study was designed to characterize the targeting properties of PEGylated and non-PEGylated TCP-1 peptides for CRC imaging. Procedures Cell uptake of cyanine 7 (Cy7)-labeled TCP-1 probes (Cy7-PEG₄-TCP-1 and Cy7-TCP-1) was investigated in three CRC cell lines (human, HCT116 and HT29; mouse, CT26). Xenograft and orthotopic CRC tumor models with HCT116 and CT26 cells were used to characterize biodistribution and CRC tumor-targeting properties of TCP-1 fluorescence and radioligand with and without PEGylation, [^99mTc]Tc-HYNIC-PEG₄-TCP-1 vs. [^99mTc]Tc-HYNIC-TCP-1. Results Fluorescence images showed that TCP-1 probes were distributed in the cytoplasm and nucleus of CRC cells. When CT26 cells were treated with unlabeled TCP-1 peptide prior to the cell incubation with Cy7-PEG₄-TCP-1, cell fluorescent signals were significantly reduced relative to the cells without blockade. Relative to Cy7-TCP-1, superior brilliance and visibility of fluorescence was observed in the tumor with Cy7-PEG₄-TCP-1 and maintained up to 18 h post-injection. [^99mTc]Tc-HYNIC-PEG₄-TCP-1 images in xenograft and orthotopic CRC models demonstrated that TCP-1 PEGylation preserved tumor-targeting capability of TCP-1, but its distribution (%ID/g) in the liver and intestine was higher than that of [^99mTc]Tc-HYNIC-TCP-1 (1.51 ± 0.29 vs 0.53 ± 0.12, P < 0.01). Better tumor visualization by [^99mTc]Tc-HYNIC-TCP-1 was observed in the orthotopic CRC model due to lower intestinal radioactivity. Conclusions TCP-1-based probes undergo endocytosis and localize in the cytoplasm and nucleus of human and mouse CRC cells. Tumor detectability of fluorescent TCP-1 peptide with a PEG₄ spacer is promising due to its enhanced tumor binding affinity and rapid clearance kinetics from nontumor tissues. Non-PEGylated [^99mTc]Tc-HYNIC-TCP-1 exhibits lower nonspecific accumulation in the liver and gastrointestinal tract and might have better capability for detecting CRC lesions in clinical sites. TCP-1 may represent an innovative targeting molecule for detecting CRC noninvasively.

Thrombosis remains a leading cause of cardiovascular morbidity and mortality. During thrombosis, activated platelets and endothelial cells expose phosphatidylserine (PS) on their outer membranes, creating a surface that accelerates clot formation. Current antithrombotic therapies, such as heparin and warfarin, carry significant bleeding risks, highlighting the need for safer alternatives. In response, we developed a PS-targeting liposomal formulation composed of Zn-dipicolylamine (DPA)-cyanine-3[22,22] and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (molar ratio 3:97). This DPA-harboring liposome (DPAL) binds selectively to PS-rich surfaces such as activated platelets and has demonstrated efficacy in reducing thrombosis in mouse models, with minimal bleeding. In the present study, we examined the interaction of DPAL with albumin, the most abundant plasma protein and a key transporter in the bloodstream, to assess the potential for harmful protein aggregation or structural disruption. Using dynamic light scattering and intrinsic protein fluorescence, we found that, unlike warfarin and heparin, DPAL does not induce any large protein aggregates or cause significant conformational changes near the tryptophan residue when mixed with human serum albumin, suggesting a favorable interaction profile. In addition, we used transwell permeability assays and CyQUANT cell proliferation assays to assess the cytotoxicity of DPAL in cultured human umbilical vein endothelial cells (HUVECs). Our results showed that DPAL does not compromise endothelial barrier integrity in HUVEC monolayers nor the cells’ viability. Our current and previous findings together suggest that DPAL could offer a promising approach to modulate harmful coagulation pathways and provide a new targeted therapeutic strategy for managing thrombotic disorders.