Increased tumor uptake of chemotherapeutics and improved chemoresponse by novel non-anticoagulant low molecular weight heparin.

Background: Recent prospective clinical trials of low molecular weight heparins (LMWHs) have demonstrated that these agents may provide significant advantages in terms of progression-free and overall survival in certain subgroups of cancer patients. The mechanisms of improved survival associated with LMWHs are not known, and may involve direct and/or indirect effects on tumor growth. The purpose of this study was to investigate the effects of LMWH and a sulfated non-anticoagulant LMWH (S-NACH) on tumor chemotherapeutic uptake and chemoresponse.

TSPO 18 kDa (PBR) Targeted Photosensitizers for Cancer Imaging (PET) and PDT.

Translocator protein (TSPO) 18 kDa overexpression has been observed in a large variety of human cancers, especially breast cancers. PK 11195, an isoquinoline analogue, is one of the ligands of highest TSPO binding affinity. Due to the long biological half life of our photosensitizers, there is a need to label them with a long lived radioisotope, for example I-124.

Exploring new applications for Rhodiola rosea: can we improve the quality of life of patients with short-term hypothyroidism induced by hormone withdrawal?

Patients treated for differentiated thyroid cancer (DTC) are subjected to periodic surveillance that includes serum thyroglobulin measurements followed by radioiodine administrations for diagnostic and therapeutic purposes if necessary. Both procedures require adequately elevated blood levels of thyroid-stimulating hormone (TSH), which can be achieved by two approaches: parenteral administration of recombinant human TSH (rhTSH) or stopping thyroid hormone replacement until optimal levels of endogenous TSH are achieved. Although rhTSH administration does not require hormone withdrawal, it is not inexpensive and carries the risk of secondary effects.

Compared to purpurinimides, the pyropheophorbide containing an iodobenzyl group showed enhanced PDT efficacy and tumor imaging (124I-PET) ability.

Two positional isomers of purpurinimide, 3-[1'-(3-iodobenzyloxyethyl)] purpurin-18-N-hexylimide methyl ester 4, in which the iodobenzyl group is present at the top half of the molecule (position-3), and a 3-(1'-hexyloxyethy)purpurin-18-N-(3-iodo-benzylimide)] methyl ester 5, where the iodobenzyl group is introduced at the bottom half (N-substitued cyclicimide) of the molecule, were derived from chlorophyll-a. The tumor uptake and phototherapeutic abilities of these isomers were compared with the pyropheophorbide analogue 1 (lead compound). These compounds were then converted into the corresponding 124I-labeled PET imaging agents with specific activity >1 Ci/micromol.

Expression of HMP/AN2, a melanoma associated antigen, in murine cerebral gliomas: potential for radioimmunotargeting.

Human melanoma proteoglycan (HMP), a melanoma-associated antigen, is expressed in both human melanomas and gliomas. We used HMP-specific monoclonal antibody (mAb) VT68.2 to investigate whether murine GL261 cerebral gliomas express the HMP homologue AN2 and to determine whether AN2 could be targeted for selective delivery of radiation in vivo.

Comparative positron-emission tomography (PET) imaging and phototherapeutic potential of 124I- labeled methyl- 3-(1'-iodobenzyloxyethyl)pyropheophorbide-a vs the corresponding glucose and galactose conjugates.

In our present study, 3-(1(')-m-iodobenzyloxyethyl)pyropheophorbide-a methyl ester 1, 3-(1'-m-iodobenzyloxyethyl)-17(2)-{(2-deoxy)glucose}pyropheophorbide-a 2, and 3-(1'-m-iodobenzyloxyethyl)-17(2)-{(1-deoxy)galactose}pyropheophorbide-a 3 were synthesized and converted into the corresponding (124)I-labeled analogues by reacting the intermediate trimethyltin analogues with Na(124)I. Photosensitizers 1-3 were evaluated for the PDT efficacy in C3H mice bearing RIF tumors at variable doses and showed a significant long-term tumor cure. Among the compounds investigated, the non-carbohydrate analogue 1 was most effective.

Relation between nodule size and 18F-FDG-PET SUV for malignant and benign pulmonary nodules.

Unlabelled: The most common semiquantitative method of evaluation of pulmonary lesions using 18F-FDG PET is FDG standardized uptake value (SUV). An SUV cutoff of 2.5 or greater has been used to differentiate between benign and malignant nodules.

Tumor immunolocalization using 124 I-iodine-labeled JAA-F11 antibody to Thomsen-Friedenreich alpha-linked antigen.

Clinical immunolocalization has been attempted by others with an anti-Thomsen-Friedenreich antigen (TF-Ag) mAb that bound both alpha- and beta-linked TF-Ag. In this report, 124 I-labeled mAb JAA-F11 specific for alpha-linked TF-Ag showed higher tumor specificity in in vivo micro-positron emission tomography (micro-PET) of the mouse mammary adenocarcinoma line, 4T1, showing no preferential uptake by the kidney. Labeled product remained localized in the tumor for at least 20 days.

Multimodality agents for tumor imaging (PET, fluorescence) and photodynamic therapy. A possible "see and treat" approach.

Methyl 3-(1'-m-iodobenzyloxyethyl)-3-devinylpyropheophorbide-a (2), obtained in a sequence of reactions from pyropheophorbide-a (a chlorophyll-a derivative), was found to be a promising imaging agent and a photosensitizer for photodynamic therapy (PDT). The electrophilic aromatic iodination of the corresponding trimethylstannyl intermediate with Na124I in the presence of an Iodogen bead afforded 124I-labeled photosensitizer 4 with >95% radioactive specificity. In addition to drug-uptake, the light fluence and fluence rate that were used for the light treatment had a significant impact in long-term tumor cure.

18F-FDG imaging: pitfalls and artifacts.

18F-FDG PET is emerging as a useful tool in the staging and restaging of many malignant neoplasms, such as lymphoma, lung cancer, colorectal cancer, head and neck cancer, breast cancer, and melanoma. To accurately interpret 18F-FDG findings one must be familiar with the normal physiologic distribution of the tracer, frequently encountered physiologic variants, and benign pathologic causes of 18F-FDG uptake that can be confused with a malignant neoplasm. The objectives of this article are to (a) describe the mechanism of 18F-FDG uptake, (b) list the patient preparation and pertinent patient history before 18F-FDG imaging, (c) describe the whole-body physiologic distribution of 18F-FDG, (d) list and discuss normal physiologic variants, and (e) list and discuss benign pathologic causes of 18F-FDG uptake.

The economic impact of 18FDG positron emission tomography in the surgical management of colorectal cancer with hepatic metastases.

Background: (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) is recognized as a powerful tool in the management of patients with recurrent and/or metastatic colorectal cancer. The aim of this was was to analyze costs from the payer's perspective, of adding FDG-PET to a computed tomography (CT) scan preoperatively in colorectal cancer patients with resectable hepatic metastases.

Methods: CT with and without FDG-PET were compared among patients with colorectal cancer in staging for surgical resection of hepatic metastases.

Gated myocardial perfusion SPECT: basic principles, technical aspects, and clinical applications.

Electrocardiographically gated myocardial perfusion SPECT (GSPECT) is a state-of-the-art technique for the combined evaluation of myocardial perfusion and left ventricular function within a single study. It is currently one of the most commonly performed cardiology procedures in a nuclear medicine department. Automation of the image processing and quantification has made this technique highly reproducible, practical, and user friendly in the clinical setting.

A Comparative Study of 511 keV SPECT and PET Using Separate 370 MBq F-18-FDG Doses on Different Days.

All previously reported comparative studies of 511 keV single-photon emission computed tomography (SPECT) and positron emission tomography (PET) have used one fluorine-18-fluorodeoxyglucose (FDG) dose, followed by PET and SPECT on the same day. This approach is inherently biased against the second imaging study. Therefore, we prospectively compared conventional PET and 511 keV SPECT in 23 patients with proven malignancy using separate 370 MBq FDG doses on different days employing an ECAT 951/31R PET scanner and a Trionix XLT-20 for SPECT.

The role of positron emission tomography in the evaluation of the N-positive neck.

Background: A major prognostic indicator in patients with squamous cell carcinoma of the upper aerodigestive tract is the presence or absence of cervical metastasis. Nodal involvement at different levels affects treatment. Thus identification of the degree of nodal involvement is important.

Positron emission tomography in the evaluation of synchronous lung lesions in patients with untreated head and neck cancer.

Background: Positron emission tomography (PET) with the glucose analogue fludeoxyglucose F 18 uses the increased glucose uptake that is observed in neoplastic cells. It can differentiate between benign and malignant pulmonary lesions in patients with lung tumors. Applications of PET in extracranial head and neck neoplasms have included evaluating patients with unknown primary lesions, detecting primary and recurrent head and neck tumors, monitoring response to radiotherapy, and evaluating the N0 neck in oral cavity carcinomas.

Clinical applications of (18)F-FDG in oncology.

PET has emerged as a powerful diagnostic tool for the evaluation of cancer patients. Currently, most of these studies are performed with the glucose analog (18)F-FDG, which has been shown to accumulate avidly in most tumors. (18)F-FDG PET is now routinely used in the diagnosis, staging, and posttherapy evaluation of oncologic patients.

Administration guidelines for radioimmunotherapy of non-Hodgkin's lymphoma with (90)Y-labeled anti-CD20 monoclonal antibody.

90Y-ibritumomab tiuxetan is a novel radioimmunotherapeutic agent recently approved for the treatment of relapsed or refractory low-grade, follicular, or CD20+ transformed non-Hodgkin's lymphoma (NHL). (90)Y-ibritumomab tiuxetan consists of a murine monoclonal antibody covalently attached to a metal chelator, which stably chelates (111)In for imaging and (90)Y for therapy. Both health care workers and patients receiving this therapy need to become familiar with how it differs from conventional chemotherapy and what, if any, safety precautions are necessary.