RESUMEN

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. Our objectives are to find translocator protein targeted photosensitizers for both tumor imaging (PET) and photodynamic therapy (PDT). I-PK 11195 is conjugated with the tumor avid photosensitizer HPPH. We find that those two tumor avid components complement each other and make the conjugate molecule even more tumor avid; compared to the photosensitizer itself, the conjugate is found to show improved PDT efficacy. It is concluded that I-PK 11195 can be a good vehicle to deliver radionuclide and photosensitizer to TSPO overexpressed tumor regions. Such conjugates could be useful for both tumor imaging (PET) and PDT.

RESUMEN

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. The latter option is simpler but induces a profound state of hypothyroidism, which results in physical and mental complaints that may interfere severely with the patient's activities of daily living. Rhodiola rosea is a popular plant in traditional medical systems in Eastern Europe and Asia with a reputation for stimulating the nervous system, decreasing depression, enhancing work performance, and eliminating fatigue, all features of clinical hypothyroidism. Investigators have also suggested additional benefits such as cardioprotection or even tumor growth inhibition. Here, we propose R. rosea as a viable alternative treatment for the symptoms of short-term hypothyroidism in patients with DTC who require hormone withdrawal.

Asunto(s)

RESUMEN

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. Among the positional isomers 4 and 5, purpurinimide 5 showed enhanced imaging and therapeutic potential. However, the lead compound 1 derived from pyropheophorbide-a exhibited the best PET imaging and PDT efficacy. For investigating the overall lipophilicity of the molecule, the 3-O-hexyl ether group present at position-3 of purpurinimide 5 was replaced with a methyl ether substituent, and the resulting product 10 showed improved tumor uptake, but due to its significantly higher uptake in the liver, spleen, and other organs, a poor tumor contrast in whole-body tumor imaging was observed.

Asunto(s)

RESUMEN

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. These results were in contrast to the in vitro data, where compared to the parent analogue the corresponding galactose and glucose derivatives showed enhanced cell kill. Among the corresponding (124)I-labeled analogues, excellent tumor images were obtained from compound 1 in both tumor models (RIF and Colon-26) and the best tumor contrast was observed at 72 h after injection. Conjugating a glucose moiety to photosensitizer 1 initially diminished its tumor uptake, whereas with time the corresponding galactose analogue showed improved tumor contrast.

Asunto(s)

RESUMEN

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. The iodo photosensitizer 2 (nonlabeled analogue of 4) produced 100% tumor cure (5/5 mice were tumor free on day 60) at a dose of 1.5 micromol/kg and a light dose of 128 J/cm2, 14 mW/cm2 for 2.5 h (lambda(max) 665 nm) at 24 h postinjection. The photosensitizer also showed promising tumor fluorescence and PET imaging ability. Our present work demonstrates the utility of the first 124I-labeled photosensitizer as a "multimodality agent", which could further be improved by using more tumor-avid and/or target-specific photosensitizers.

Asunto(s)

RESUMEN

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. Outcomes included uncomplicated surgery, complicated surgery, or death. Extrahepatic disease occurrence rates and diagnostic accuracy of CT and FDG-PET were obtained from published sources. Complication rates and costs for CT, FDG-PET, and surgical procedures were obtained from Healthcare Finance Administration data. RESULTS: The average expected surgical cost per patient when FDG-PET was used to determine the presence of extrahepatic disease was 16,278 dollars compared to 21,547 dollars for conventional management-a net savings of 5,269 dollars. CONCLUSIONS: Integration of FDG-PET into the presurgical evaluation of patients with hepatic metastases could substantially reduce overall costs and patients' morbidity. This substantial net saving results from the unique ability of FDG-PET in excluding patients with extrahepatic disease, and avoiding unnecessary surgical expenses.

Asunto(s)

RESUMEN

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. In patients with coronary artery disease, gating enhances the diagnostic and prognostic capability of myocardial perfusion imaging, provides incremental information over the perfusion data, and has shown potentials for myocardial viability assessment and sequential follow-up after therapy. After reading this article, the readers will understand (a) the general principles of GSPECT and quantitation, (b) the methods of the image acquisition and analysis, (c) validation of GSPECT with other cardiac imaging modalities, and (d) application of the GSPECT-derived functional parameters in the clinical practice.

Asunto(s)

RESUMEN

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. Evaluation of the neck by conventional imaging modalities (computed tomography or magnetic resonance imaging) is not completely accurate. Positron emission tomography (PET) scanning as a dynamic functional assessment may allow detection of multiple metastatic nodes at different levels. PURPOSE: We sought to compare the effectiveness of PET with pathologic examination for: presence, location, and number of cervical metastases in the clinically N-positive neck. SETTING: Tertiary care academic facility. Materials and methods From 1994 to 1997, 15 patients with clinically N-positive necks who had preoperative PET scans underwent 23 neck dissections. PET scans were correlated with the pathologic findings of the neck dissections in determining the ability to correctly identify the number and level(s) of nodal disease. RESULTS: When determining identification of the level of disease, PET demonstrated sensitivity of 81%; specificity, 99%; positive predictive value, 97%; negative predictive value, 90%; and accuracy, 92%. When evaluating the ability to correctly predict neck stage, PET demonstrated sensitivity of 86%, positive predictive value of 100%, and accuracy of 80% compared with clinical examination with sensitivity of 53% and accuracy of 53%. CONCLUSION: PET accurately identified disease in the N-positive neck. Its ability to identify multiple level disease may allow it to help predict the selectivity of neck dissection in the therapeutic protocol.

Asunto(s)

RESUMEN

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. After reading this paper, the reader should understand the physiologic basis of using (18)F-FDG in patients with different tumors, describe the role of this radiopharmaceutical in the management of oncologic patients, and identify those malignancies for which (18)F-FDG has proved to be effective in diagnosis and follow-up.

Asunto(s)

RESUMEN

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. Because (90)Y is a pure beta-emitter, the requisite safety precautions are not overly burdensome for health care workers or for patients and their families. (90)Y-ibritumomab tiuxetan is dosed on the basis of the patient's body weight and baseline platelet count; dosimetry is not required for determining the therapeutic dose in patients meeting eligibility criteria similar to those used in clinical trials, such as <25% lymphomatous involvement of the bone marrow. (111)In- and (90)Y-ibritumomab tiuxetan are labeled at commercial radiopharmacies and delivered for on-site dose preparation and administration. Plastic and acrylic materials are appropriate for shielding during dose preparation and administration; primary lead shielding should be avoided because of the potential exposure risk from bremsstrahlung. Because there are no penetrating gamma-emissions associated with the therapy, (90)Y-ibritumomab tiuxetan is routinely administered on an outpatient basis. Furthermore, the risk of radiation exposure to patients' family members has been shown to be in the range of background radiation, even without restrictions on contact. There is therefore no need to determine activity limits or dose rate limits before patients who have been treated with (90)Y radioimmunotherapy are released, as is necessary with patients who have been treated with radiopharmaceuticals that contain (131)I. Standard universal precautions for handling body fluids are recommended for health care workers and patients and their family members after (90)Y-ibritumomab tiuxetan administration. In summary, (90)Y-ibritumomab tiuxetan introduces (90)Y into clinical practice and expands the role nuclear medicine plays in the care of patients with cancer. Understanding the unique properties of this novel radioimmunoconjugate will facilitate its safe and effective use.

Asunto(s)