Development of Iodinated Indocyanine Green Analogs as a Strategy for Targeted Therapy of Liver Cancer.

Liver cancer is one of the leading causes of cancer-related deaths, with a significant increase in incidence worldwide. Novel therapies are needed to address this unmet clinical need. Indocyanine green (ICG) is a broadly used fluorescence-guided surgery (FGS) agent for liver tumor resection and has significant potential for conversion to a targeted therapy.

Upregulation of Somatostatin Receptor Type 2 Improves 177Lu-DOTATATE Therapy in Receptor-Deficient Pancreatic Neuroendocrine Tumor Model.

Pancreatic neuroendocrine tumors (PNET) express high levels of somatostatin receptor type 2 (SSTR2), a unique target for both tumor imaging and therapy. This surface expression is lost in metastatic high-grade PNETs, making patients ineligible for SSTR2-targeted 177 Lutetium (Lu)-DOTATATE peptide receptor radionuclide therapy (PRRT), and represents an unmet clinical need. Here, we aimed to restore SSTR2 expression through the reversal of inhibitory epigenetic gene silencing to improve tumor responsiveness to PRRT.

Site-Specifically Conjugated Single-Domain Antibody Successfully Identifies Glypican-3-Expressing Liver Cancer by Immuno-PET.

Primary liver cancer is the third leading cause of cancer-related deaths, and its incidence and mortality are increasing worldwide. Hepatocellular carcinoma (HCC) accounts for 80% of primary liver cancer cases. Glypican-3 (GPC3) is a heparan sulfate proteoglycan that histopathologically defines HCC and represents an attractive tumor-selective marker for radiopharmaceutical imaging and therapy for this disease.

Rubella virus IgM and IgG antibodies with avidity in pregnant women and outcomes at a tertiary facility in Ghana.

Background: Congenital rubella syndrome (CRS) is a recognised cause of childhood deafness and blindness caused by the transplacental transmission of rubella virus during pregnancy. Women in the reproductive age group, and by extension their unborn babies may therefore be at increased risk. The prevalence of Rubella virus specific IgM and IgG antibodies, including IgG avidity, was determined in pregnant women attending the antenatal clinic at a Teaching Hospital in Ghana.

Ac-MACROPATATE: A Novel α-Particle Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors.

Neuroendocrine tumors (NETs) express somatostatin receptors (SSTRs) 2 and 5. Modified variants of somatostatin, the cognate ligand for SSTR2 and SSTR5, are used in treatment for metastatic and locoregional disease. Peptide receptor radionuclide therapy with Lu-DOTATATE (DOTA-octreotate), a β-particle-emitting somatostatin derivative, has demonstrated survival benefit in patients with SSTR-positive NETs.

Impacted dentures in the pharynx and esophagus Implication for advocacy.

Background: Impaction of dentures has potentially significant morbidity and management challenges. This study sought to leverage on the occurrence of swallowed dentures to advance discussions on its management and prevention.

Methods: A 5-year retrospective review of patients seen on account of impacted dentures at the Ear, Nose, and Throat Department of the Korle-Bu Teaching Hospital was done.

HBZmacropa-NCS: A Bifunctional Chelator for Actinium-225 Targeted Alpha Therapy.

Actinium-225 (Ac) is one of the most promising radionuclides for targeted alpha therapy (TAT). With a half-life of 9.92 days and a decay chain that emits four high-energy α particles, Ac is well-suited for TAT when conjugated to macromolecular targeting vectors that exhibit extended in vivo circulation times.

Towards the stable chelation of radium for biomedical applications with an 18-membered macrocyclic ligand.

Targeted alpha therapy is an emerging strategy for the treatment of disseminated cancer. [Ra]RaCl is the only clinically approved alpha particle-emitting drug, and it is used to treat castrate-resistant prostate cancer bone metastases, to which [Ra]Ra localizes. To specifically direct [Ra]Ra to non-osseous disease sites, chelation and conjugation to a cancer-targeting moiety is necessary.

AfHNS fellowship: Model to improve access to head and neck cancer care in Africa and developing countries.

Background: Head and neck cancers occur predominantly in developing countries where access to care is poor. Sub-Saharan Africa has <20 head and neck surgeons for >1 billion people and has only two fellowship training programs.

Methods And Results: The AfHNS Head and Neck Fellowship is being introduced to accelerate training of African surgeons to improve access to resource appropriate cancer care.

Sodium Fluoride-18 and Radium-223 Dichloride Uptake Colocalize in Osteoblastic Mouse Xenograft Tumors.

Patients with osteoblastic bone metastases are candidates for radium-223 (RaCl) therapy and may undergo sodium fluoride-18 (F-NaF) positron emission tomography-computed tomography imaging to identify bone lesions. F-NaF has been shown to predict RaCl uptake, but intratumor distributions of these two agents remain unclear. In this study, the authors evaluate the spatial distribution and relative uptakes of F-NaF and RaCl in Hu09-H3 human osteosarcoma mouse xenograft tumors at macroscopic and microscopic levels to better quantify their correlation.

Glypican-3-Targeted Alpha Particle Therapy for Hepatocellular Carcinoma.

Glypican-3 (GPC3) is expressed in 75% of hepatocellular carcinoma (HCC), but not normal liver, making it a promising HCC therapeutic target. GC33 is a full-length humanized monoclonal IgG1 specific to GPC3 that can localize to HCC in vivo. GC33 alone failed to demonstrate therapeutic efficacy when evaluated in patients with HCC; however, we posit that cytotoxic functionalization of the antibody with therapeutic radionuclides, may be warranted.

Genotypic Characterization of Epstein Barr Virus in Blood of Patients with Suspected Nasopharyngeal Carcinoma in Ghana.

Nasopharyngeal cancer (NPC) is associated with Epstein Barr virus (EBV) infection. However different viral strains have been implicated in NPC worldwide. This study aimed to detect and characterize EBV in patients diagnosed with NPC in Ghana.

Is AJCC/UICC Staging Still Appropriate for Head and Neck Cancers in Developing Countries?

By 2030, 70% of cancers will occur in developing countries. Head and neck cancers are primarily a developing world disease. While anatomical location and the extent of cancers are central to defining prognosis and staging, the American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) have incorporated nonanatomic factors that correlate with prognosis into staging (eg, p16 status of oropharyngeal cancers).

African Head and Neck Society Clinical Practice guidelines for thyroid nodules and cancer in developing countries and limited resource settings.

Background: International thyroid nodule and cancer management guidelines generally fail to take into account potential limitations in diagnostic and treatment resources.

Methods: Thyroid cancer specialists from the African Head and Neck Society and American Head & Neck Society Endocrine Section developed guidelines for diagnosis and management of thyroid nodules and cancer in low resource settings. Recommendations were based on literature review and expert opinion, with level of evidence defined.

ImmunoPET Predicts Response to Met-targeted Radioligand Therapy in Models of Pancreatic Cancer Resistant to Met Kinase Inhibitors.

: Pancreatic ductal adenocarcinoma (PDAC) has limited standard of care therapeutic options. While initially received with enthusiasm, results from targeted therapy with small molecule tyrosine kinases inhibitors (TKIs) have been mixed, in part due to poor patient selection and compensatory changes in signaling networks upon blockade of one or more kinase of tumors. Here, we demonstrate that in PDACs otherwise resistant to rational kinase inhibition, Met-directed immuno-positron emission tomography (immunoPET) can identify targets for cell-signaling independent targeted radioligand therapy (RLT).

A Study of 219Rn Outgassing and 211Pb Contamination from 223Ra In dry, Liquid, and Murine Tissue Samples.

Introduction: A study of Pb contamination caused by the outgassing of Rn from Ra in dry, liquid, and murine tissues samples has been made to help design proper handling procedures for Ra in preclinical biodistribution work.

Materials And Methods: Pb activity levels were measured from Ra in dry, liquid, and tissue samples using aspiration and autoradiography techniques.

Results: Using aspiration techniques on dry samples of Ra, an average Rn outgassing rate of 51% ± 21% was measured with one measurement reaching as high as 81%.

Preclinical Evaluation of Pb-Labeled Low-Molecular-Weight Compounds for Targeted Radiopharmaceutical Therapy of Prostate Cancer.

Targeted radiopharmaceutical therapy (TRT) using α-particle radiation is a promising approach for treating both large and micrometastatic lesions. We developed prostate-specific membrane antigen (PSMA)-targeted low-molecular-weight agents for Pb-based TRT of patients with prostate cancer (PC) by evaluating the matching γ-emitting surrogate, Pb. Five rationally designed low-molecular-weight ligands (L1-L5) were synthesized using the lysine-urea-glutamate scaffold, and PSMA inhibition constants were determined.

African head and neck fellowships: A model for a sustainable impact on head and neck cancer care in developing countries.

Background: There is an extreme shortage of head and neck surgeons in Africa. Fourteen head and neck surgeons have completed fellowships in Cape Town and Cameroon. This study determines whether such Africa-based fellowships are a good model for developing countries by making a sustainable impact on head and neck cancer care.

Exploration of a F(ab') Fragment as the Targeting Agent of α-Radiation Therapy: A Comparison of the Therapeutic Benefit of Intraperitoneal and Intravenous Administered Radioimmunotherapy.

Refinement of treatment regimens enlisting targeted α-radiation therapy (TAT) is an ongoing effort. Among the variables to consider are the target molecule, radionuclide, dosage, and administration route. The panitumumab F(ab') fragment targeting epidermal growth factor receptor tolerated modification with the TCMC chelate as well as radiolabeling with Pb or Pb.

Comparative studies on the therapeutic benefit of targeted α-particle radiation therapy for the treatment of disseminated intraperitoneal disease.

Identification of the appropriate combination of radionuclide, target and targeting vehicle is critical for successful radioimmunotherapy. For the treatment of disseminated peritoneal diseases such as pancreatic or ovarian cancer, α-emitting radionuclides have been proposed for targeted radiation therapy. This laboratory has taken a systematic approach investigating targeted α-radiation therapy, allowing comparisons to now be made between At, Th, Bi and Pb.

Targeted α-Particle Radiation Therapy of HER1-Positive Disseminated Intraperitoneal Disease: An Investigation of the Human Anti-EGFR Monoclonal Antibody, Panitumumab.

Identifying molecular targets and an appropriate targeting vehicle, i.e., monoclonal antibodies (mAb) and their various forms, for radioimmunotherapy (RIT) remains an active area of research.

Does concurrent chemoradiotherapy preceded by chemotherapy improve survival in locally advanced nasopharyngeal cancer patients? Experience from Ghana.

Background: To find out how chemotherapy given prior to concurrent chemoradiotherapy compares with concurrent chemoradiation alone in the treatment of locally advanced nasopharyngeal cancer.

Methods: Patient charts were examined and found to have submitted to one of two regimes as follows: Neoadjuvant chemotherapy consisting of Cisplatin and 5-fluorouracil followed by concurrent chemoradiotherapy with cisplatin (group1), or concurrent cisplatin based chemoradiotherapy only (group 2). Radiation treatment dose of 70Gy in 35 fractions was given in each group.

Cell Killing Mechanisms and Impact on Gene Expression by Gemcitabine and 212Pb-Trastuzumab Treatment in a Disseminated i.p. Tumor Model.

In pre-clinical studies, combination therapy with gemcitabine and targeted radioimmunotherapy (RIT) using 212Pb-trastuzumab showed tremendous therapeutic potential in the LS-174T tumor xenograft model of disseminated intraperitoneal disease. To better understand the underlying molecular basis for the observed cell killing efficacy, gene expression profiling was performed after a 24 h exposure to 212Pb-trastuzumab upon gemcitabine (Gem) pre-treatment in this model. DNA damage response genes in tumors were quantified using a real time quantitative PCR array (qRT-PCR array) covering 84 genes.

Unexpected Behavior of the Heaviest Halogen Astatine in the Nucleophilic Substitution of Aryliodonium Salts.

Aryliodonium salts have become precursors of choice for the synthesis of (18) F-labeled tracers for nuclear imaging. However, little is known on the reactivity of these compounds with heavy halides, that is, radioiodide and astatide, at the radiotracer scale. In the first comparative study of radiohalogenation of aryliodonium salts with (125) I(-) and (211) At(-) , initial experiments on a model compound highlight the higher reactivity of astatide compared to iodide, which could not be anticipated from the trends previously observed within the halogen series.

(2S)-2-(3-(1-Carboxy-5-(4-211At-Astatobenzamido)Pentyl)Ureido)-Pentanedioic Acid for PSMA-Targeted α-Particle Radiopharmaceutical Therapy.

Unlabelled: Alpha-particle emitters have a high linear energy transfer and short range, offering the potential for treating micrometastases while sparing normal tissues. We developed a urea-based, At-labeled small molecule targeting prostate-specific membrane antigen (PSMA) for the treatment of micrometastases due to prostate cancer (PC).

Methods: PSMA-targeted (2S)-2-(3-(1-carboxy-5-(4-At-astatobenzamido)pentyl)ureido)-pentanedioic acid (At- 6: ) was synthesized.