Targeted radiopharmaceutical therapy for advanced lung cancer: phase I trial of rhenium Re188 P2045, a somatostatin analog.

Background: Both small cell and non-small cell lung cancer overexpress somatostatin receptors (SSTR). P2045 peptide is an 11-amino acid somatostatin analog that binds with high affinity to SSTR and can be labeled with Tc-99m to gauge receptor prevalence or with Re-188 for 2.1 MeV beta radiotherapy.

Tumor-targeted HPMA copolymer-(RGDfK)-(CHX-A''-DTPA) conjugates show increased kidney accumulation.

N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-RGDfK conjugates targeting the alpha(v)beta(3) integrin have shown increased accumulation in solid tumors and promise for selective delivery of radiotherapeutics to sites of angiogenesis- or tumor-expressed alpha(v)beta(3) integrin. An unresolved issue in targeting radiotherapeutics to solid tumors is toxicity to non-target organs. To reduce toxicity of radiolabeled conjugates, we have synthesized HPMA copolymer-RGDfK conjugates with varying molecular weight and charge content to help identify a polymeric structure that maximizes tumor accumulation while rapidly clearing from non-targeted organs.

An assessment of radionuclidic impurities of (210)Po produced via neutron irradiation of (209)Bi for use in targeted alpha-particle radiotherapy.

Radionuclidic impurities of (210)Po prepared by neutron irradiation of (209)Bi via the (209)Bi(n,gamma)(210)Bi reaction were investigated. Following irradiation and ingrowth, a pure (210)Po solution was obtained by sublimation and dissolution. Results were obtained by liquid scintillation (LS) counting, isotope dilution alpha (alpha)-spectrometry, and high-purity germanium gamma-ray spectrometry.

Nanocarriers for nuclear imaging and radiotherapy of cancer.

Several nanoscale carriers (nanoparticles, liposomes, water-soluble polymers, micelles and dendrimers) have been developed for targeted delivery of cancer diagnostic and therapeutic agents. These carriers can selectively target cancer sites and carry large payloads, thereby improving cancer detection and therapy effectiveness. Further, the combination of newer nuclear imaging techniques providing high sensitivity and spatial resolution such as dual modality imaging with positron emission tomography/computed tomography (PET/CT) and use of nanoscale devices to carry diagnostic and therapeutic radionuclides with high target specificity can enable more accurate detection, staging and therapy planning of cancer.

Polymeric conjugates of mono- and bi-cyclic alphaVbeta3 binding peptides for tumor targeting.

The alphaVbeta3 integrin plays important roles in tumor-induced angiogenesis and tumor metastasis and hence, many small molecule alphaVbeta3 ligands have been developed for cancer diagnosis and therapy. Although these show good alphaVbeta3 targeting, most have suboptimal pharmacokinetics and show rapid tumor washout. We studied the biodistribution and tumor targeting properties of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer based conjugates of mono-(RGDfK) and doubly cyclized (RGD4C) alphaVbeta3 binding peptides.

Comparison of imaging with FDG PET/CT with other imaging modalities in myeloma.

Objective: To determine the usefulness of FDG PET/CT scanning in the management and staging of myeloma and to assess its strengths and limitations.

Design: FDG PET/CT scans and all other available imaging studies were reviewed retrospectively from 16 consecutive patients by two experienced musculoskeletal radiologists and two nuclear medicine physicians working in consensus.

Patients: The 16 patients had undergone a total of 19 FDG PET/CT scans.

Polymer-peptide conjugates for angiogenesis targeted tumor radiotherapy.

Introduction: New methods of delivering radiotherapy to sites of occult or disseminated cancer are needed to control the disease and address the failure of conventional therapy. Because tumor cells rely on angiogenesis for survival, we assessed the effectiveness of beta-emitter radiotherapy delivered by polymer-peptide conjugates that target tumor neovasculature. This molecularly targeted radiation is intended to damage both the endothelial bed and surrounding neoplastic cells.

Comparison of 2-dimensional and 3-dimensional acquisition for 18F-FDG PET oncology studies performed on an LSO-based scanner.

Unlabelled: Three-dimensional (3D) PET acquisition has the potential to reduce image noise but the advantage of 3D PET for studies outside the brain has not been well established. To compare the performance of 2-dimensional (2D) and 3D acquisition for whole-body (18)F-FDG applications, a series of patient studies were performed using a lutetium oxyorthosilicate (LSO)-based tomograph.

Methods: Comparative 2D and 3D images were acquired for 27 oncology patients using an LSO-based tomograph.

Bone scintigraphy of calciphylaxis: a syndrome of vascular calcification and skin necrosis.

Calciphylaxis is a highly morbid syndrome of vascular calcification and skin necrosis, the pathophysiology of which remains largely elusive. We report a patient with end-stage renal disease and multiple painful skin lesions who underwent a bone scan for extremity pain. Increased tracer accumulation was seen in the subcutaneous tissues of the trunk and lower extremities.

Targeting tumor angiogenesis: comparison of peptide and polymer-peptide conjugates.

Unlabelled: Endothelial cells in tumor angiogenesis are highly accessible, genetically stable and present unique molecular markers for targeted therapy. Neoplasia is also characterized by enhanced vascular permeability and disordered lymphatics so that both active and passive targeting strategies may play a role in localizing angiogenesis-targeted agents. To investigate the relative importance of these targeting strategies, the tissue biodistribution of both endothelial-specific and nonspecific peptides and their macromolecular peptide-copolymer conjugates were studied in 2 xenograft models of prostate cancer.

Targeting tumor angiogenic vasculature using polymer-RGD conjugates.

Sites of neovascular angiogenesis are important chemotherapy targets. In this study, the synthesis, characterization, in-vivo imaging and biodistribution of a technetium-99m labeled, water-soluble, N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer carrying doubly cyclized Arg-Gly-Asp motifs (HPMA copolymer-RGD4C conjugate) are reported. In vitro endothelial cell adhesion assays indicated that HPMA copolymer-RGD4C conjugates inhibited alphaVbeta3-mediated endothelial cell adhesion while HPMA copolymer Arg-Gly-Glu control conjugates (HPMA copolymer-RGE4C conjugate) and hydrolyzed HPMA copolymer precursor (HPMA copolymer) showed no activity.

Technetium-99m-Labeled N-(2-hydroxypropyl) methacrylamide copolymers: synthesis, characterization, and in vivo biodistribution.

Purpose: To synthesize novel technetium-99m (99mTc)-labeled N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers and characterize the effect of charge and molecular weight on their biodistribution in SCID mice.

Methods: Electronegative and neutral 7-kDa, 21-kDa, and 70-kDa HPMA copolymers containing a 99mTc chelating comonomer, bearing N-omega-bis(2-pyridylmethyl)-L-lysine (DPK), were synthesized by free-radical precipitation copolymerization. The copolymers were labeled via 99mTc tricarbonyl chelation to DPK-bearing comonomer.

Evaluation of human anti-mouse antibody response in normal volunteers following repeated injections of fanolesomab (NeutroSpec), a murine anti-CD15 IgM monoclonal antibody for imaging infection.

Background: Fanolesomab (NeutroSpec) is a murine monoclonal Tc labelled anti-CD15 IgM antibody that localizes collections of human polymorphonuclear neutrophils (PMNs) at sites of infection.

Objectives: The objectives of this study were to evaluate the safety of repeated injections of fanolesomab and the extent of induction of human anti-mouse antibody (HAMA) response.

Methods: Thirty healthy adults (15 men and 15 women) were enrolled in the study.

Positron emission tomography scanning for the diagnosis and management of lung cancer.

The dissemination of positron emission tomography (PET) technology has enabled a functional approach to the evaluation of lung cancer that complements the anatomic assessment provided by chest radiography, computed tomography (CT) scanning, and magnetic resonance imaging. PET has excellent sensitivity and good specificity for the determination of malignancy in the solitary pulmonary nodule, but these data must be weighed against the evidence of instances of false-positive results because of inflammatory lesions and false-negative results in small- or low-metabolism neoplasms. Therefore, PET may not be advisable when these scenarios apply.

Physical aspects of yttrium-90 microsphere therapy for nonresectable hepatic tumors.

Administration of yttrium-90 microspheres via the hepatic artery is an attractive approach to selectively deliver therapeutic doses of radiation to liver malignancies. This procedure allows delivering radiation absorbed doses in excess of 100 Gy to the tumors without significant liver toxicity. The microsphere therapy involves different specialties including medical oncology, radiation oncology, nuclear medicine, interventional radiology, medical physics, and radiation safety.

99m Tc anti-CD 15 monoclonal antibody (LeuTech) imaging improves diagnostic accuracy and clinical management in patients with equivocal presentation of appendicitis.

Background: Appendicitis frequently presents in an atypical fashion leading to misdiagnosis or a delay in diagnosis. This is particularly true in early cases where the patient may be erroneously discharged from an emergency department and will invariably return with perforated appendicitis. The standard of care is hospital admission for observation or early operation.