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In this report, we describe a method for quantitative bone scan interpretation (the Bone Scan Index or BSI) in advanced prostate cancer. The BSI estimates the fraction of the skeleton that is involved by tumor, as well as the regional distribution of the metastases in the bones. The purpose of this report is to describe the development and validation of this method in terms of reproducibility and the application of BSI for determining extent of disease and monitoring disease progression. We analyzed 263 bone scans from 90 patients being studied under four protocols at Memorial Sloan-Kettering Cancer Center for progressive, androgen-independent prostate cancer (AIPC), who had bone scans as a part of their work-up. We determined: (a) the intraobserver and interobserver variability of the BSI; (b) the comparison between a change in BSI and prostate-specific antigen (PSA); (c) the regional distribution of bony metastases in early stage D prostate cancer (3% skeletal involvement); and (d) the rate of growth of bony metastases from prostate cancer. A cube root transformation of the percentage of involvement of the entire skeleton was used to stabilize the variance over the entire span of values (0-60% tumor involvement). The range of interobserver variability between readers was 0.2-0.5 times the cube root of the BSI (69 scans, 18 patients). Intraobserver variability was minimal when the same reader read the same scans after a 2-year interval, showing a correlation coefficient of 0.97 (reader 1) and 0.99 (reader 2), P0.001. There was a parallel rise in the BSI and the PSA in 24 patients (105 scans) treated for AIPC with hydrocortisone followed by suramin at PSA relapse (Pearson's moment correlation, 0.71). In a group of 27 patients with limited bone involvement by AIPC (i.e.,3% BSI), the distribution of early metastases was not random within the skeleton but was distributed in the central skeleton in a manner that matched the distribution of the normal adult bone marrow. Also, in a group of 21 patients (62 scans), the change in BSI as a function of time after diagnosis was explored graphically. The progression of bone scan changes in AIPC, from early involvement (3%) to late involvement, was fitted to a Gompertzian equation. It showed a rapid exponential growth phase, with an estimated tumor doubling time of 43 days when the BSI was 3.3%. The change in BSI rapidly approached a more gradual slope as the percentage of skeletal involvement increased. The BSI provides a reproducible new parameter for quantitative assessment of bone involvement by AIPC. These results suggest that the BSI will be useful for stratifying patients entering treatment protocols for extent of tumor involvement of bone. Although further study is necessary, serial bone scan BSI appears capable of quantifying both the progression of bony involvement by tumor as well as the response to treatment.

To assess the tumor targeting, safety, and efficacy of monoclonal antibody 131I-labeled CC49 in patients with androgen-independent prostate cancer, 16 patients received 75 mCi/m2 of the radiolabeled antibody after 7 days of IFN-gamma pretreatment. Sequential tumor biopsies in three patients showed a median 5-fold (range, 2-6-fold) increase in the proportion of cells staining positively for the TAG-72 antigen, whereas one showed a decrease in staining. Fourteen patients received 131I-labeled CC49, whereas 2 showed a disease-related decrease in performance status, precluding antibody treatment. The antibody localized to sites of metastatic androgen-independent prostate cancer in 86% (12 of 14; 95% confidence interval, 57-95%) of cases. Both osseous and extraosseous sites were visualized, and in six (42%) patients, more areas were visible when the radioimmunoconjugate was used than were apparent when conventional scanning techniques were used. The localization of the conjugate in the marrow cavity was usually a site not visualized by the radionuclide bone scan, in which the isotope localizes primarily to the tumor-bone interface. The dose-limiting toxicity was thrombocytopenia because five (36%) patients showed grade IV and seven (50%) showed grade III effects. In addition, six (42%) patients, four of whom were hospitalized, showed a flare in baseline pain, and four showed a decrease in pain. No patient showed a50% decline in prostate-specific antigen, although radionuclide bone scans remained stable in four cases for a median of 4 months. The results are consistent with dosimetry estimates showing that the delivered dose to tumor was subtherapeutic and suggest that approaches that exclusively target the bone tumor interface or the marrow stroma may be unable to completely eradicate disease in the marrow cavity. For CC49, improving outcomes would require repetitive dosing, which was precluded by the rapid development of a human antimouse antibody response.

It is common protocol in radionuclide therapies to administer a tracer dose of a radiopharmaceutical, determine its lesion uptake and biodistribution by gamma imaging, and then use this information to determine the most effective therapeutic dose. This treatment planning approach can be used to quantitate accurately the activity and volume of lesions and organs with positron emission tomography (PET). In this article, the authors focus on the specification of appropriate volumes of interest (VoI) using PET in association with computed tomography (CT).The authors have developed an automatic image segmentation schema to determine the VoI of metastases to the lung from PET images, under conditions of variable background activity. An elliptical Jaszczak phantom containing a set of spheres with volumes ranging from 0.4 to 5.5 mL was filled with F-18 activity (2-3 microCi/mL) corresponding to activities clinically observed in lung lesions. Images were acquired with a cold background and then with variable source-to-background (S/B) ratios of: 7.4, 5.5, 3.1, and 2.8. Lesion VoI analysis was performed on 10 patients with 17 primary or metastatic lung lesions, applying the optimum threshold values derived from the phantom experiments. Initial volume estimates for lung lesions were determined from CT images. Approximate S/B ratios were obtained for the corresponding lesions on F-18-fluoro-2-deoxy-D-glucose (18FDG)-PET images. From the CT estimate of the lesion size and the PET estimate of the S/B ratio, the appropriate optimum threshold could be chosen. The threshold was applied to the PET images to obtain lesion activity and a final estimate of the lesion volume.Phantom data analysis showed that image segmentation converged to a fixed threshold value (from 36% to 44%) for sphere volumes larger than 4 mL, with the exact value depending on the S/B ratios. For patients, the use of optimum threshold schema demonstrated a good correlation (r = 0.999) between the initial volume from CT and the final volume derived from the 18FDG-PET scan (P0.02). The mean difference for those volumes was 8.4%.The adaptive thresholding method applied to PET scans enables the definition of tumor VoI, which hopefully leads to accurate tumor dosimetry. This method can also be applied to small lesions (4 mL). It should enable physicians to track objectively changes in disease status that could otherwise be obscured by the uncertainties in the region-of-interest drawing, even when the scans are delineated by the same physician.

The degree of tumor necrosis after preoperative intravenous chemotherapy is likely to be an indicator of prognosis for patients with primary osteosarcoma. This study was undertaken to evaluate the efficacy of thallium-201 (Tl-201) scintigraphy in assessing response to chemotherapy in patients with osteosarcoma and to correlate the findings with the degree of tumor necrosis assessed histologically.Twenty-four patients with biopsy-proven osteosarcoma underwent Tl-201 imaging before and immediately after preoperative intravenous chemotherapy. The maximum pixel counts taken over the tumor divided by those taken of a background region yielded a tumor-to-background ratio. The percentage of change in the tumor-to-background ratio before and after chemotherapy, defined as the alteration ratio, was correlated with the percentage of tumor necrosis. The percentages of tumor necrosis were classified into 4 grades: Grade 1,50%; Grade 2, 50-89%; Grade 3, 90- 99%; Grade 4, 100%.Three patients with Grade 1 histologic response had an alteration ratio of 31% +/- 4 (mean +/- standard deviation). Three patients with Grade 2 response had an alteration ratio of 76% +/- 9. Nine patients with Grade 3 response had an alteration ratio of 84% +/- 11. Nine patients with Grade 4 response had an alteration ratio of 96% +/- 5. These ratios correlated well with the histologic grades (P0.001).The results of this study suggest that Tl-201 scintigraphy is a powerful tool in the evaluation of tumor response to chemotherapy in patients with osteosarcoma.

Heterotopia of the gray matter is a developmental malformation in which ectopic cortex is found in the white matter of the brain. A case of a 33-year-old man with cortical heterotopia who had a lifelong history of seizures and psychomotor retardation is reported, including the results of cerebral CT, magnetic resonance imaging, and positron emission tomography using 18F-2-deoxyglucose.

The origin of radiotherapy dates back to 1895-immediately after the discovery of X-rays. Since the beginning, efforts were focused on developing ways to improve the accuracy of radiation delivery. Molecular imaging allows the visualization of surrogates of several pathophysiological characteristics of tumor tissue (e.g., proliferation, metabolism, hypoxia, perfusion), allowing tailoring of dose distribution based on the tissue's features and biological patterns within the tumor. A significant improvement in the ability of modern radiotherapy to precisely target tumor while avoiding irradiating normal tissues can be achieved by integrating molecular imaging into an individualized radiation treatment planning. PET data are the most common molecular images used for tumor volume delineation and assessment of pathophysiological characteristics of tissue. The type of radiopharmaceutical used allows visualization and understanding of different pathophysiologic information. The most commonly used among all PET tracers is the 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG). [18F]FDG is currently the mainstay of PET use in radiotherapy. With the aim of identifying specific biological tumor processes and offering valuable information that can assist radiation oncologist to modulate radiotherapy's doses and volumes, several other molecular imaging tracers emerged in the last few years. Non-[18F]FDG tracers commonly used in radiation oncology include [11C]Methionine ([11C]MET) for brain tumors; [18F]FDOPA for brain and neuroendocrine tumors; radiolabeled somatostatin analogs for somatostatin-receptor positive tumors; 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) and 18F-fluoromisonidazole (18F-FMISO) to identify regions of radiation resistance within the tumor; and [11C]/[18F]Choline, [18F]/68Ga-PSMA, and 18F-Fluciclovine for prostate cancer.

The armamentarium of approved radiopharmaceuticals for either diagnosis or therapy is at the core of the clinical practice of today's nuclear medicine. Nevertheless, both because the currently approved agents do not meet all the clinical needs for radionuclide targeting and because advancing knowledge in the pathophysiology of tissues/organs opens in turn new opportunities, investigations continue at the preclinical and clinical validation level for the development of new radiopharmaceuticals, most of which are not approved yet for commercial use. Concerning in particular the diagnostic applications of nuclear medicine to oncology, ongoing investigations in the search for tumor-targeting agents with better specificity and sensitivity are countless, possibly within the scenario of theranostics-that is, with the dual potential for imaging and for therapy, depending on the specific radionuclide employed for radiolabeling. We will focus this chapter on the most promising imaging agents labeled with single-photon-emitting radionuclides based on some of the mechanisms that are typical for tumor cells/tissues.

Monoclonal antibodies (MAbs) raised against cancer antigens may mediate antibody-dependent cell-mediated cytotoxicity. This form of cancer control arises from cytolysis of a target cell by effector lymphocytes, such as cytotoxic T lymphocytes or natural killer cells. However, most of these antibodies have low/moderate efficacy in the tumor control. Antibodies targeting hormone receptors expressed by cancer have shown greater tumor control compared with other cell membrane targets. Moreover, the labeling of these antibodies with a toxin can potentiate their efficacy in the tumor control. In this way, the antibody becomes an invaluable targeting vector for delivery of the toxin to the cancer cells. The toxin/antibody complex is called the immunoconjugate. Different molecules, chemicals, or radioisotopes can serve themselves as toxins; toxins may have long half-lives in the body (e.g., ricin), thus increasing the toxicity to both the cancer and normal tissues. However, the different radioisotopes (e.g., iodine-131, lutetium-177) have a wide range of half-lives and radiation decay that make them useful for different applications. Beta-emitting radioisotopes, predominantly I-131, have had only modest success in radioimmunotherapy. More recently, high linear energy transfer (LET) radiation in the form of alpha particles has been studied: alpha radiation is ideal for killing isolated cancer cells in transit in the vascular and lymphatic systems and regressing tumors by disruption of tumor capillary networks by targeting and killing tumor capillary endothelial cells. Over the past 20 years the development of alpha-immunoconjugates has enabled targeted alpha therapy (TAT) to progress from in vitro studies, through in vivo experiments, to clinical trials. The dose to normal tissues always provides a limitation to the injected dose and that received by the tumor. However, TAT can achieve cancer regression within the maximum tolerance dose for normal tissue. TAT was originally thought to be an ideal therapy for "liquid" cancers, e.g., leukemia and micro-metastases, as the short half-lives of the radioisotopes were sufficient to target these cancer cells and the short range ensured that the targeted cancer cells received the highest radiation dose. Different antibodies have been developed and tested in clinical trials as conditioning treatment, but none of them have yet been approved for radioimmunotherapy (RIT) in multiple myeloma (MM). Addiotinally, bone-seeking radiopharmaceuticals are being evaluated in MM patients in the transplant setting.

Multiple myeloma (MM) represents about 1.8% of all cancers and 10% of all hematologic malignancies. MM is the most common primary bone cancer. The clonal proliferation of malignant plasma cells in the bone marrow may result both in local growth and in systemic effects due to the overproduction of a monoclonal protein (M-protein). Plasma cell proliferation is linked to a variety of clinical presentations of the disease, ranging from simple monoclonal gammopathy of undetermined significance (MGUS) to smoldering myeloma (SMM) to full-blown "malignant" MM. MM differs from MGUS and SMM by the presence of the end-organ damage associated with a complex syndrome named CRAB. However, in the updated version of the criteria for the diagnosis of plasma cell proliferative disorders established by the International Myeloma Working Group (IMWG), more specific criteria have been established to define MM, MGUS, and SMM. Excess bone marrow plasma cells, M-protein, osteolytic bone lesions, renal disease, and immunodeficiency constitute the pathophysiologic bases of the clinical manifestations of MM. Severe bone pain, pathologic fractures, spinal cord compression, and hypercalcemia are caused by lytic bone lesions. The course of MM is highly variable, and the clinical behavior is remarkably heterogeneous. Many studies have identified prognostic factors capable of predicting this heterogeneity in survival (serum β2-microglobulin, albumin, C-reactive protein, and lactate dehydrogenase). The standard workup of MM is based on a number of laboratory tests that are utilized for risk stratification. The International Staging System (ISS) is a powerful and reproducible three-stage classification in which the ISS3 class is associated with the poorest outcome. Imaging studies demonstrate the extent and severity of bone involvement (intramedullary/extramedullary, site and number of lesions) at baseline, including disease-related complications, such as pathologic fractures; they also serve to assess response to treatment and provide follow-up surveillance. The ISS introduced over 25 years ago is mainly based on serum β2-microglobulin and albumin levels, without any reference to the presence of bone lesions or to the methodology employed for their evaluation. Although the ISS serves as a prognostic indicator rather than as an accurate scoring system, it adequately estimates tumor burden and risk stratification, allowing differentiation of MGUS and SMM from MM. In 1975, Durie and Salmon introduced a clinical staging system based on the presence of bone lesions to grade the severity of the disease. While the original Durie and Salmon system was essentially based on the use of planar X-ray for evaluating bones, a newer version, the PLUS system, was released in 2005 to improve the accuracy of staging with advanced imaging modalities such as [18F]FDG-PET/CT and MRI.

Leukemias are a group of acute and chronic hematological neoplasias characterized by the dissemination of cancer cells originating in the bone marrow via the bloodstream. In 2016, the estimated number of new leukemia cases was more than 110,000 in all of Europe and 47,000 in the USA. Leukemia is the cause of 4% of all cancer deaths and accounts for 3.6% of all cancers. Historically, leukemias have been divided into four major categories further classified into subtypes based on specific features of cells: acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myelogenous leukemia (AML), and chronic myelogenous leukemia (CML). A revised classification of myeloid/lymphoid neoplasms and leukemias has recently been published to better characterize each disease. This updated classification incorporated new scientific and clinical information to refine diagnostic criteria for previously described neoplasms and introduced newly recognized disease entities. In this chapter, the main entities of leukemia, with specific regard to imaging for diagnosis, treatment response assessment, and follow-up, will be treated according to what is reported in the clinical guidelines.

Molecular targeting requires assessing several factors that come into play such as the location of the target, the choice of radionuclide, the inertness of the bifunctional chelate and stability of the covalently bound halogens, matching the residence time in the tumor with the physical half-life of the radionuclide, the scale and scope of the disease, and the absorbed dose sensitivity of the targeted tumor compared to normal tissue. The principles of molecular targeting are well established, but a paradigm shift from designing a medium-affinity radiotracer used to determine target density to designing a high-affinity, high-target density radioligand to maximize the target-to-nontarget ratio should increase the probability of detecting lesions smaller than the instrument resolution. Developing and validating a therapeutic radiopharmaceutical for a single target is necessary, but often not sufficient to produce a toxic event because of other mechanisms that are only partially understood. These include nontargeted effects due to radiation emitted from neighboring, targeted cells as well as bystander effects produced by the cellular processing of radiation not necessarily impinging on DNA. Both of these indirect consequences of cellular radiation could make a substantial contribution to the efficacy of targeted radionuclide therapy. These mechanisms should be exploited to optimize the efficacy of targeted radiotherapy and overcome the inefficiency of tumor control due to nonuniform distribution of radiation dose. The design approach to take advantage of the indirect consequences of cellular radiation depends heavily on further elucidation of the indirect effect. The successful combination of these two should lead to more effective nuclear radiotherapy.

Radiopharmaceuticals contain a radionuclide and an agent to direct the radionuclide to a receptor, antigen, ionic pump, or other sites of interest. Some radiopharmaceuticals are simple, such as the ionic form of the radionuclide, while most radiopharmaceuticals have a complex chemical structure where the radionuclide provides a signal, indicating the site of localization of the carrier molecule. Common single-photon radiopharmaceuticals used for oncological diagnosis include the agents labeled with 99mTc such as 99mTc-bisphosphonates (that accumulate at sites of bone mineral deposition), 99mTc-labeled colloids (that are used for lymphoscintigraphy and for imaging of the liver and spleen), 99mTc-hexakis-methoxy-isobutyl-isonitrile, and 99mTc-tetrofosmin (initially employed for myocardial perfusion imaging, and also used for localization of parathyroid adenomas and for identification of other malignant tumors). The most commonly used radiopharmaceuticals labeled with radioiodine (123I or 131I) include iodide itself (for localization of thyroid tissue) and the catecholamine analog metaiodobenzylguanidine (MIBG, for localizing pheochromocytoma and neuroblastoma). Thallium-201 chloride (201Tl) is used for myocardial perfusion imaging as well as tumor perfusion imaging, while 111In-pentetreotide detects overexpression of somatostatin receptors, especially in neuroendocrine tumors and in lesions arising from the neural crest, such as carcinoid, paragangliomas, and medullary thyroid carcinomas. 111In-capromab pendetide is a murine monoclonal antibody recognizing a transmembrane glycoprotein expressed by poorly differentiated and metastatic prostate adenocarcinomas. 67Ga-citrate receptors are overexpressed on membranes of both tumor and inflammatory cells.

Radiopharmaceuticals contain a radionuclide and an agent to direct the radionuclide to a receptor, antigen, ionic pump, or other sites of interest. Some radiopharmaceuticals are simple, such as the ionic form of the radionuclide, while most radiopharmaceuticals have a complex chemical structure where the radionuclide provides a signal, indicating the site of localization of the carrier molecule. Common single-photon radiopharmaceuticals used for oncological diagnosis include the agents labeled with 99mTc such as 99mTcbisphosphonates (that accumulate at sites of bone mineral deposition), 99mTc-labeled colloids (that are used for lymphoscintigraphy and for imaging of the liver and spleen), 99mTc-hexakis-methoxy-isobutyl-isonitrile, and 99mTc-tetrofosmin (initially employed for myocardial perfusion imaging, and also used for localization of parathyroid adenomas and for identification of other malignant tumors). The most commonly used radiopharmaceuticals labeled with radioiodine (123I or 131I) include iodide itself (for localization of thyroid tissue) and the catecholamine analog metaiodobenzylguanidine (MIBG, for localizing pheochromocytoma and neuroblastoma). Thallium-201 chloride (201Tl) is used for myocardial perfusion imaging as well as tumor perfusion imaging, while 111In-pentetreotide detects overexpression of somatostatin receptors, especially in neuroendocrine tumors and in lesions arising from the neural crest, such as carcinoid, paragangliomas, and medullary thyroid carcinomas. 111In-capromab pendetide is a murine monoclonal antibody recognizing a transmembrane glycoprotein expressed by poorly differentiated and metastatic prostate adenocarcinomas. 67Ga-citrate receptors are overexpressed on membranes of both tumor and inflammatory cells.

Multiple myeloma represents about 1.8% of all cancers and 10% of all hematologic malignancies. Multiple myeloma (MM) is the most common primary bone cancer. The clonal proliferation of malignant plasma cells in the bone marrow may result both in local growth and in systemic effects due to the overproduction of a monoclonal protein (M-protein). Plasma cell proliferation is linked to a variety of clinical presentations of the disease, ranging from simple monoclonal gammopathy of undetermined significance (MGUS) to smoldering myeloma (SMM) to full-blown "malignant" MM. MM differs from MGUS and SMM by the presence of the end-organ damage associated with a complex syndrome named CRAB. However, in the updated version of the criteria for the diagnosis of plasma cell proliferative disorders established by the International Myeloma Working Group (IMWG), more specific criteria have been established to define MM, MGUS, and SMM. Excess bone marrow plasmacells, M-protein, osteolytic bone lesions, renal disease, and immunodeficiency constitute the pathophysiologic bases of the clinical manifestations of MM. Severe bone pain, pathologic fractures, spinal cord compression, and hypercalcemia are caused by lytic bone lesions. The course of MMis highly variable, and the clinical behavior is remarkably heterogeneous. Many studies have identified prognostic factors capable of predicting this heterogeneity in survival (serum β2-microglobulin, albumin, C-reactive protein, and lactate dehydrogenase). The standard workup of MM is based on a number of laboratory tests that are utilized for risk stratification. The International Staging System (ISS) is a powerful and reproducible three-stage classification in which the ISS3 class is associated with the poorest outcome. Imaging studies demonstrate the extent and severity of bone involvement (intramedullary/extramedullary, site and number of lesions) at baseline, including disease- related complications, such as pathologic fractures; they also serve to assess response to treatment and provide follow-up surveillance. The ISS introduced over 25 years ago is mainly based on serum β2-microglobulin and albumin levels, without any reference to the presence of bone lesions or to the methodology employed for their evaluation. Although the ISS serves as a prognostic indicator rather than as an accurate scoring system, it adequately estimates tumor burden and risk stratification, allowing differentiation of MGUS and SMM from MM. In 1975 Durie and Salmon introduced a clinical staging system based on the presence of bone lesions to grade the severity of the disease. While the original Durie and Salmon system was essentially based on the use of planar x-ray for evaluating bones, a newer version, the PLUS system was released in 2005 to improve the accuracy of staging with advanced imaging modalities such as [18F]FDG-PET/CT, and MRI.

Leukemias are a group of acute and chronic hematological neoplasias characterized by the dissemination of the cancer cells originating in the bone marrow via the bloodstream. In 2016 the estimated number of new leukemia cases was more than 110,000 in all of Europe and 47,000 in the USA. Leukemias, cause of 4% of all cancer deaths and account for 3.6% of all cancers. Historically, leukemias have been divided into four major categories further classified into subtypes based on specific features of cells: acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myelogenous leukemia (AML), and chronic myelogenous leukemia (CML). A revised classification of myeloid/lymphoid neoplasms and leukemias has recently been published to better characterize each disease. This updated classification incorporated new scientific and clinical information to refine diagnostic criteria for previously described neoplasms and introduced newly recognized disease entities. In this chapter the main entities of leukemia, with specific regard to imaging for diagnosis, treatment response assessment, and follow-up, will be treated according to what reported in the clinical guidelines.

Purpose: To assess the clinical accuracy of whole-body 2-[F-18]-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) in the diagnosis of recurrent colorectal carcinoma in comparison to conventional computed tomography (CT).Materials and methods: Forty patients with suspected recurrent colorectal carcinoma based on either progressive serial carcinoemrbyonic antigen (CEA) serum elevation or positive/equivocal CT findings underwent whole-body FDG-PET. PET results were compared with those of CT and correlated to the final histopathological and clinical findings.Results: A final diagnosis was obtained at 93 sites in 35 patients by histology and in 5 patients by clinical follow up of at least 6 months. Of the 93 sites, 53 were determined to be malignant and 40 benign. FDG-PET evaluated on a 5-point scale (0-4) showed a positive and negative predictive value in the range of 96-98% and 83-93% respectively as the threshold for positivity was moved from 0 through 3. By comparison, CT, also evaluated on a 5-point scale showed a positive and negative predictive value in the range of 75-88% and 67-71% respectively. The area under the fitted receiver operating characteristic curve for PET: A(PET) = 0.96 +/- 0.02 was significantly greater (P < 0.001) than that observed for CT: A(CT) = 0.77 +/- 0.06. The distribution of maximum standardized uptake value (SUVmax) showed that all negative lesions have SUVmax below 5.0 whereas 75% of positive lesions were above 5.0 pointing to the fact that disease positivity is more likely in lesions with high SUV values.Conclusion: The results of this study confirm that whole-body FDG-PET is more accurate than conventional CT in the staging of patients with suspected recurrent colorectal carcinoma.

Fourteen F-18 fluorodeoxyglucose (FDG) studies were carried out in 13 patients known to have bony metastases from carcinoma of the prostate. One patient was newly diagnosed. The remaining patients had various types of therapy and were considered hormonally resistant. The average age was 67. All patients had extensive bony metastases shown on the conventional Tc99m-MDP bone scans. Only about 18% of bony lesions apparent on the conventional bone scans showed corresponding increase of FDG uptake. Anatomical correlation was performed by using co-registered images of SPECT and PET in the same area. The positive FDG uptake was not related to the duration of illness, level of PSA, previous therapy, and magnitude of disease involvement. It appears that only a small percentage of bony metastases is associated with increased glycolysis. It is possible that other metabolic processes are more important than glycolysis for providing prostate cancer with a source of energy and nutrients.

We present a case of metastatic carcinoid tumor metastatic to the heart, presenting as ventricular arrhythmia and diagnosed by 111Inpentetreotide scintiscan despite negative endocardial biopsy. The incidence and diagnosis of carcinoid heart disease is discussed, as well as the complementary role of high-resolution anatomical images (CT, MRI) with functional images (SPECT, PET) to determine the correct diagnosis of this rare condition.

Two human immunoglobulin M (IgM) monoclonal antibodies (MoAbs), 16.88 and 28A32, which react with cytoplasmic (28A32 and 16.88) or cell surface (28A32) determinants on human colon carcinoma cells, were administered intravenously to 26 patients with metastatic colorectal carcinoma to determine if they could localize to sites of metastatic disease, if they had any antitumor or toxic effects, and to determine whether they would elicit an antihuman MoAb response. Serial scans showed tumor uptake of radioisotope in 12 of 16 patients receiving 131I-labeled 28A32 and in nine of 12 patients receiving 131I-labeled 16.88. No antitumor effects were seen with either antibody. No antibody-related toxic effects were observed following administration of 16.88, but two patients developed localized urticarial reactions following injection with antibody 28A32. No patient developed an antibody response to 16.88. Anti-28A32 reactivity was found in five of 12 (42%) normal sera and in seven of 23 (30%) patients before receiving any antibody. Following administration of 28A32, a low titer (1:10 dilution) of anti-28A32 developed in four patients with no preexisting antibody, a decrease in the preexisting titer was seen in three other patients, the titer remained constant in one patient, and no anti-28A32 was ever detected in six patients. In most cases, anti-28A32 activity was lost at dilutions greater than 1:10 and did not appear to affect antibody half-life in the serum or whole body retention of the antibody. We conclude that these human IgM MoAbs are capable of localizing at sites of disease in vivo, are nontoxic, and are poorly immunogenic in humans. Further studies to determine the specificity of targeting and to improve the delivery of antibody to sites of tumor are indicated.

Labeling of plasma transferrin with gallium was investigated to determine whether the gallium-transferrin complex could be effectively used as a macromolecular tracer in studies of capillary permeability using Positron Emission Tomography (PET). Three gallium-plasma preparations were tested and 2 h bio-distribution studies were performed in rats. The three preparations gave similar blood clearance and tissue distribution data, but the methods used for evaluating gallium-transferrin binding were found to be suboptimal. Gallium clearance from blood was biexponential with both components faster than that of 125I-albumin. Gallium distribution spaces in all tissues including intracerebral Walker-256 tumors were larger than those of albumin. These results indicate a relative instability of the gallium-transferrin complex in vivo, which appears to preclude its use as an acceptable radiolabeled protein for vascular permeability studies using PET.

The measurement of glucose utilization rate (GUR) by positron emission tomography (PET) using 18F-2-fluoro-2-deoxy-D-glucose (FDG) is a valuable method to assess the grade of malignancy of brain tumors. We have designed a feasibility trial to determine whether PET could be used to image and predict the grade of malignancy of human extremity musculoskeletal tumors. Five patients with extremity tumors (four soft-tissue tumors and one osteogenic tumor) were studied. Peak and mean apparent GURs were determined in the tumor region. All tumors were subsequently resected and graded in a standard fashion using the NCI grading system. Peak apparent GURs ranged from 3.3 mg/100 g/min to 15.2 mg/100 g/min, with the highest values found in the high grade tumors. Although the number of patients studied was small, a good correspondence was shown between GURs and histopathologic grading. Our results indicate that PET can be used to image and evaluate the metabolic activity of human musculoskeletal tumors.

PURPOSE: To evaluate the prognostic significance of a bone scan index (BSI) based on the weighted proportion of tumor involvement in individual bones, in relation to other factors and to survival in patients with androgen-independent prostate cancer. PATIENTS AND METHODS: Baseline radionuclide bone scans were reviewed in 191 assessable patients with androgen-independent disease who were enrolled onto an open, randomized trial of liarozole versus prednisone. The extent of skeletal involvement was assessed by scoring each scan using the BSI and independently according to the number of metastatic lesions. The relationship of the scored bone involvement to other known prognostic factors was explored in single- and multiple-variable analyses. RESULTS: In single-variable analyses, the pretreatment factors found to be associated with survival were age (P = .0446), performance status (P = .0005), baseline prostate-specific antigen (P = .0001), hemoglobin (P = .0001), alkaline phosphatase (P = .0002), AST (P = .0021), lactate dehydrogenase (P = .0001), and treatment (P = .0098). The extent of osseous disease was significant using both the BSI (P = .0001) and the number of lesions present (P = .0001). In multiple-variable proportional hazards analyses, only BSI, age, hemoglobin, lactate dehydrogenase, and treatment arm were associated with survival. When the patient population was divided into three equal groups, with BSI values of < 1.4%, 1.4% to 5.1%, and > 5.1%, median survivals of 18.3, 15.5, and 8.1 months, respectively, were observed (P = .0079). CONCLUSION: The BSI quantifies the extent of skeletal involvement by tumor. It allows the identification of patients with distinct prognoses for stratification in clinical trials. Further study is needed to assess the utility of serial BSI determinations in monitoring treatment effects. The BSI may be particularly useful in the evaluation of agents for which prostate-specific antigen changes do not reflect clinical outcomes accurately.

Experience of scintigraphic detection of bone lesion and active bone marrow involvement of multiple myeloma, especially with sestamibi and FDG-PET scans is in evolution. We report a case of intense sestamibi uptake in bone marrow correlating with the extent of the disease, while FDG-PET scans showed activity only in areas of active disease progression associated with pain. Technetium-99m-sestamibi appears to indicate the extent of the disease, while [18F]FDG-PET scans show sites of active tumor proliferation and may be useful in directing local therapy such as radiation.