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Bast RC Jr, Kufe DW, Pollock RE, et al., editors. Holland-Frei Cancer Medicine. 5th edition. Hamilton (ON): BC Decker; 2000.

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Holland-Frei Cancer Medicine. 5th edition.

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Chapter 30HRadionuclide Imaging in Cancer Medicine

, MD, PhD.

Radionuclide evaluations of cancer have been a major emphasis of nuclear medicine practice and research for decades. While methods, techniques, and applications have changed dramatically over the years, the fundamental goals of applying radionuclide methods to cancer detection and diagnosis, staging, and treatment monitoring, in addition to some direct therapeutic applications, have continued to guide research and clinical practice with these techniques.

While primarily a diagnostic modality, radionuclide methods are also used therapeutically. Except for in vitro methods, such as radioimmunoassay (RIA), radionuclide applications in cancer involve the administration (usually intravenously) of a labeled compound of biologic interest. The label is an isotope with a decay scheme that facilitates detection and imaging with gamma camera systems, or the more specialized technique of positron emission tomography (PET).

Some of the first radionuclide applications in cancer, including the use of iodine isotopes for diagnosis and treatment of thyroid carcinomas and other thyroid abnormalities, remain important parts of radionuclide cancer applications today, even though the diagnostic environment in which these methods are now employed is quite different from the one that existed when the methods were first developed.

Advances in radionuclide methods in cancer medicine have occurred along two parallel paths: (1) radiochemistry developments, and (2) new imaging methods. While new imaging developments, including software and hardware applications related to standard gamma camera imaging, single photon emission computed tomography (SPECT), and PET, have fundamentally altered and improved radionuclide approaches to cancer detection and treatment, the direction of basic and clinical research in this field, including hardware design, has been determined largely by advances in radiochemistry.

It is convenient to divide radiochemistry and hardware methods in radionuclide imaging into two categories: (1) “single photon” methods based on commonly used isotopes including, technitium 99m (Tc 99m), iodine-131 (I-131), (T1-201), and others that produce a variety of detectable decay products (primarily gamma photons in the energy range of about 75–300 KeV); and (2) “dual photon” techniques employing positron emitting isotopes (e.g., F-18, N-13, C-11, and O-15).

Positron producing isotopes emit a positively charged electron (e1), which, after traveling a short distance through tissue, undergoes annihilation with a negatively charged electron (e2), resulting in the emission of two oppositely directed 511-KeV photons. These two antiparallel 511-KeV photons can be detected external to the body by PET systems. PET units consist of rings of solid-state detectors designed to detect the annihilation photons more or less “simultaneously” or, in some systems, to use small differences in arrival times at the detectors in the image reconstruction process (“time-of-flight devices”).

For simplicity, in the remainder of this section these two different approaches to radionuclide imaging will be as (1) “gamma camera methods” (including the gamma camera method known as SPECT), and (2) PET methods.

In addition to research and development in radiopharmaceuticals and imaging devices, another feature in the development of radionuclide applications for cancer medicine is the evolution of a better understanding of relationships between radionuclide methods and cancer biology (e.g., studies of the relationships between in vivo cancer metabolism, as defined by imaging techniques, and in vitro indicators of malignant potential, such as cellular oncogene expression). Modern image-processing methods have also made possible the systematic combination of other imaging modalities (such as projectional radiologic images of “plain films,” ultrasonography, computed tomography [CT], and magnetic resonance imaging [MRI]) with radionuclide methods through computer-based (digital) techniques that produce three-dimensional images to reflect physiology and biochemistry (by radionuclide methods), as well as anatomy (by CT, MRI, and other methods). It is now possible, therefore, to visualize function as well as anatomy of cancer in vivo with a level of precision not previously attainable before the advent of modern digital imaging methods.

Gamma Camera Methods Including SPECT

Standard nuclear medicine techniques, as practiced at virtually every major hospital in the United States, continue to comprise the bulk of cancer-related radionuclide applications. Space does not permit a comprehensive review of these applications, but some issues of current and future relevance are identified in the following sections.

Bone Scanning

Radionuclide evaluation of the skeletal system (bone scanning) remains one of the most useful diagnostic methods in cancer medicine.1–3 The radiopharmaceutical in widest use (Tc 99m methylene diphosphonate, or MDP), can be produced easily in nuclear medicine laboratories, and focal MDP uptake is related to skeletal osteoblastic activity. While its molecular mechanism of binding to bone is not as clearly defined as that of the positron emitter F-18 (fluoride) ion, which exchanges with hydroxyl ions in the hydroxyapatite crystal, MDP is a sensitive indicator of bone metabolic activity and continues to be used extensively in planar and SPECT-imaging studies of the skeletal system, particularly for radionuclide metastatic surveys.

The present relatively widespread availability of SPECT systems makes it possible to generate tomographic (transverse, coronal, and sagittal) images of skeletal structures within the field of view of the gamma camera (i.e., approximately 14–17 inches in diameter). Whole body skeletal surveys are still performed usually in a planar, nontomographic mode. Since SPECT requires additional imaging time for equal volumes of tissue, compared with planar radionuclide techniques, routine whole-body SPECT surveys would be too time consuming with currently available systems.

It has been recognized for decades that MDP bone scans are very sensitive but not highly specific indicators of altered bone metabolism. Approximately 50% of the local bone mass must be lost before lesions can be seen on plain radiographs, and bone scans are abnormal long before that. However, abnormal uptake on a bone scan can occur in disease processes besides cancer, including inflammatory, traumatic, and metabolic conditions. Therefore, plain films are used routinely during the initial reviews of bone scans to increase the specificity of the results. Additional imaging methods (CT and MRI) can be used as needed to better define the conditions underlying the abnormalities that are seen on bone scans.

The development of more sophisticated biochemical methods for cancer detection and diagnosis has also had an impact on in vivo imaging methods. It is now known, for example, that the likelihood of an abnormal bone scan is low in a patient with prostatic carcinoma when the prostate-specific antigen (PSA) is under 10 μg/L.4,5 Therefore, bone scanning can now be used more selectively in patients with prostate cancer. At the same time, the better definition and anatomic precision of SPECT may help identify patients with critically located metastases, such as those who are at risk for developing pathologic fractures.

In addition to radionuclide bone scanning and plain radiographs, other skeletal-imaging methods, particularly CT and MRI, are very useful for evaluating the skeletal system. The resolution of CT and its sensitivity to calcium density within tissues makes it particularly useful for identifying cortical bone abnormalities. MRI is similarly useful for detecting metastases in the marrow cavity as well as selected cortical and trabecular bone abnormalities. Some studies have indicated that MRI has a higher sensitivity, overall, than radionuclide scans for detecting bone metastases.6–8 Nevertheless, properly performed radionuclide bone scans remain useful because of their relatively low cost and because they offer options for whole-body surveys and SPECT imaging (see above).

An important therapeutic application of radionuclides in the skeletal system is the use of β-emitting radiopharmaceuticals for pain relief in patients with widespread skeletal metastases. Strontium-89 has been approved by the U.S. Food and Drug Administration (FDA) for use in this context, and several other bone-seeking radiopharmaceuticals that emit β particles are also under evaluation for radiation therapy of skeletal metastases.9–11 Two of these agents, rhenium-186 HEDP and samarium-153 EDTMP (both now in phase III trials) also emit gamma photons in an energy range that is suitable for gamma camera imaging, which helps to ascertain the distribution of the administered radiopharmaceutical.

While this approach to treatment will not help patients who have pathologic fractures, it can be useful for pain relief in patients with otherwise uncomplicated bone metastases. Bone scanning with MDP can also be a useful method for identifying appropriate patients for this form of therapy. Studies have shown that while life expectancy does not appear to be lengthened significantly by the treatment, the therapeutic radionuclides can lessen skeletal pain considerably in patients with end-stage skeletal involvement by cancer. To date, these agents have been used most widely in patients with widespread prostate cancer metastases, but they have also been applied to patients with skeletal metastases from cancer of the breast, lung, and other organ systems. Clinical monitoring of the platelet and leukocyte counts during and after therapy is necessary, as well as adherence to standard dosimetry protocols for administration of the radioactive agents.9–11

Thyroid

The treatment of remnants of functioning tissues within the thyroid bed with oral I-131 following total thyroidectomy for thyroid cancer, as well as the treatment of disease recurrence and metastases with I-131, remain standard approaches in this disease. The requirements of I-131 treatment include histologic and/or imaging evidence that the tumor actually metabolizes I-131 (as do most papillary or follicular carcinomas of the thyroid, whereas medullary carcinomas of the thyroid do not).12–14 The non–β-emitting isotope of iodine I-123 is the agent of choice for simple diagnostic evaluations of iodine uptake by the thyroid. In thyroid cancer patients, however, I-131 is still widely used as a diagnostic scanning agent. The long physical half-life of 8 days makes it possible to image patients several days after the compound is administered, permitting clearance of the agent and resulting in better contrast of tumor, compared with background tissues.

As with PSA determinations in prostate cancer patients, evaluating serum thyroglobulin concentrations15 may be a useful indicator of the presence of cancerous thyroid tissue in the body. I-131 imaging is used primarily to guide I-131 treatment. In the absence of abnormal uptake of I-131 on diagnostic scans, the likelihood of a good treatment response to I-131 is lower.

Gallium, Thallium, and Other Nonspecific Tumor Tracers

Gallium-67 citrate and thallium-201 chloride are two well-known single-photon radiopharmaceuticals that have been used traditionally for locating neoplastic or inflammatory foci (gallium) and for myocardial perfusion imaging (thallium). Gallium-67 citrate remains a useful tumor localization agent, particularly for lymphomas, but its use has been somewhat limited by its relatively complex biodistribution pattern. The radiopharmaceutical has an affinity for iron-binding proteins (ferritin, lactoferrin, bacterial siderophores, and others), is actively excreted through the mucosa of the gastrointestinal tract, undergoes urinary excretion as well, and has a significant amount of normal marrow uptake. As a result, it is often necessary to image gallium distribution 24 to 72 hours after administration; this makes it a relatively time-consuming but still useful test.16,17

Thallium has demonstrated utility as a myocardial perfusion agent. It has also attracted attention recently as a useful biochemical marker for the presence of viable tumor tissue with several neoplasms, including brain tumors, breast cancer, and others.18–20 Thallium, in addition to being taken up by tissues in proportion to their blood perfusion, is also concentrated by the (Na1-K1) -adenosine triphosphatase (ATPase) pump and is an indicator of tumor viability. Black et al.18 have shown that SPECT brain imaging of astrocytomas with thallium-201 produces results that correlate with the histologic grade of lesions. They report that the method can identify tumor recurrences, complementing the information available from contrast-enhanced CT or MRI scans. While PET imaging with the glucose analogue 2-[F-18] fluoro-2-deoxy-d-glucose (FDG) is a more precise method for this application (see below), thallium-201 SPECT can produce useful studies when PET is not available.

Both thallium-201 and another agent that is used for myocardial perfusion imaging, Tc 99m sestamibi, have been employed to identify primary lesions and nodal metastases from breast cancer.19,21,22,23,24 Tc 99m sestamibi has also been demonstrated to be a substance for the P-glycoprotein mdr gene transporter.25

Receptor-targeted Imaging Methods

A particularly appealing approach to radionuclide applications in cancer medicine is the design of radiolabeled macromolecules that are targeted to specific receptors on cancer cells. These approaches have both diagnostic and therapeutic potential, and they can be used potentially with gamma camera (including SPECT) and with PET imaging.

Imaging and therapy with monoclonal antibodies (mAb) were made possible with the development of the hybridoma technique by Kohler and Milstein.26 While research on the use of mAb for the diagnosis and treatment of cancer has grown enormously since their discovery, early expectations that the field would yield “magic bullets” analogous to I-131 for the treatment of thyroid cancer have remained largely unrealized for two reasons:27 (1) most available mAbs are currently of murine origin, resulting in the production of human antimouse antibodies (HAMA) by patients who are treated with repeated administrations of the mAbs. This produces lower plasma concentrations of the mAb than might be necessary to achieve a therapeutic effect; and (2) the cellular heterogeneity of cancer cells results in variable recognition of the cells by a given mAb. Partial solutions to the former problem have been pursued by developing immunogenic (Fab) fragments and “humanized” mAb.28,29

The mAb used in imaging have been labeled primarily with iodine-131, indium-111, iodine-123, and technetium 99m. As discussed by Goldenberg,30 three “generations” of labeled mAbs have been studied, including (1) first-generation whole immunoglobulin G (IgG) molecules labeled with I-131; (2) second-generation whole IgG molecules labeled with In-111; and (3) third-generation Tc 99m labeled antibody fragments (bivalent F(ab')2 and monovalent Fab' and Fab fragments). These third-generation products are less immunogenic, resulting in a decreased HAMA response. They are also cleared from the general circulation more quickly; higher ratios of tumor to background can, therefore, be reached earlier following injection than with first- and second-generation agents, thus facilitating tumor detection with imaging. Additional physical advantages are the wide availability and relatively low cost of Tc 99m as a label (virtually all hospitals have access to Tc 99m generators) and the better gamma camera—imaging characteristics of Tc 99m (greater number of photons for external detection and lower absorbed radiation dose), compared with the other isotopes listed above.

Several excellent reviews of the clinical experience with mAb imaging for cancer detection are available.30–32 These agents have shown good potential in a variety of published series, including their ability to identify primary tumors and metastases that have not been found with anatomic imaging techniques (CT and MRI). Nevertheless, labeled mAb have not yet achieved the status of routine clinical use.

Reports of clinical experience with mAb imaging in a wide variety of cancers are available, including cancers of the colon, ovary, prostate, breast, lung, and liver, as well as trophoblastic and germ cell tumors, lymphomas, melanoma, and neuroblastoma.31 Goldenberg estimates that approximately 60 to 90% of identified lesions in the published studies have been pinpointed correctly by mAb imaging (termed “RAID” for radioimmunodetection). The largest clinical experience, to date, has been acquired with colorectal and ovarian cancers.30

In addition to imaging, cancer therapy (radioimmunotherapy or “RAIT”) has also shown promise with mAb.30–37 The studies of therapeutic applications have used mAb conjugated with drugs (chemotherapeutic agents), toxins, or β-emitting radiopharmaceuticals.30,31 The difficult challenge faced by RAIT remains achieving a high enough local concentration of labeled mAb to deliver effective levels of therapeutic radiation. Isotopes emitting β particles (electrons) are potentially well suited for this task. Depending on their energy, the path lengths of these ionizing particles may be relatively short (e.g., < 1 mm for the β particle from I-131).

In addition to the physical characteristics of a given isotope, other critical factors affecting tumor dosimetry from RAIT include the residence time of the labeled antibody at its target, the relative affinity of the antibody for tumor cells (taking into account the immunologic heterogeneity of many tumors), and the rate of clearance from normal tissues (which affects the therapeutic ratio, or the dose delivered to the tumor, compared with the dose delivered to normal tissues).

Order and colleagues34 were the first to use a form of RAIT (I-131 antiferritin antibodies for hepatocellular cancer patients); recent work has indicated that lymphomas and leukemias may be the most suitable tumor systems for RAIT.30,35

Other Receptor-targeted Agents

Receptor-targeted imaging with other agents besides mAbs is another exciting developmental application for radionuclide in cancer medicine. This area of research also has potential relevance to treatment as well as to diagnosis of the increasing sophistication of radiolabeling procedures, along with advances in our understanding of the molecular biology of cancer.38 Mab technology makes it possible to target specific tumor receptors, such as the epidermal growth factor receptor (EGF) with mAb,39 and parallel progress with non-mAb methods is now occurring. Metabolite and receptor-targeted imaging with PET has already achieved clinically significant results (see below).

Examples of non-mAb receptor-targeted methods are the imaging and treatment of tumors that express somatostatin receptors using the somatostatin analogue octreotide (Novartis).40 A variety of neuroendocrine tumors, including insulinomas, carcinoids, vasoactive intestinal peptide-secreting tumors, glucagohomas, and gastrinomas, have somatostatin receptors. Octreotide is more resistant to enzymatic degradation than is somatostatin and, therefore, has a longer plasma half-life than somatostatin itself. Octreotide has been evaluated both as a potential therapeutic agent for gastrointestinal endocrine tumors41 and (using a modified form of octreotide, in which the phenylalanine at position 3 is replaced by tyrosine) as an imaging agent.41,42

Kvols et al.42 found that 22 of 28 patients with carcinoids and islet cell tumors had positive uptake of I-123 octreotide. In a larger series of neuroendocrine and non-neuroendocrine tumors that had somastatin receptors, the same research group demonstrated the effectiveness of octreotide for imaging; they also reported a positive correlation between the scans and subsequent responses to treatment with radiolabeled octreotide in some patients.43

These promising results with octreotide explain the current widespread interest in developing other peptide agents as diagnostic tools for oncology. These agents again have potential utility not just for cancer detection but also for monitoring of therapy and for new therapeutic strategies based on receptor-binding characteristics.

Positron Emission Tomography

PET, which was initially developed and applied primarily for neurologic and cardiac applications,44 is now used widely as both an investigative and a clinical tool in cancer medicine.45–50 While PET differs from gamma camera radionuclide methods in terms of the detector systems and the radiopharmaceuticals used (see above), it shared with gamma camera methods the fundamental approach of quantifying and mapping the distribution in vivo of administered radiopharmaceuticals. Table 30H.1 is a partial list of some of the positron-emitting radiopharmaceuticals that have been used for investigative and clinical applications with PET in oncology.

Table 30H.1. Radiopharmaceuticals Used for PET Studies of Cancer.

Table 30H.1

Radiopharmaceuticals Used for PET Studies of Cancer.

PET applications in cancer medicine have been focused on three clinical goals: (1) detection and diagnosis; (2) staging; and (3) treatment monitoring. Paralleling these clinical goals, basic investigations are being pursued to develop better PET methods that are specific for cancer and, more fundamentally, to use PET as a tool for achieving a better understanding of cancer biology.

The observation by Otto Warburg in 1930 that malignant transformation of cells is associated with an increased glycolytic rate (even in the presence of oxygen)51,52 has stimulated many of the current PET studies. F-18-fluorodeoxy-glucose (FDG), a metabolite analogue that was initially developed in the form of C-14 deoxyglucose to evaluate cerebral glucose metabolism by Sokoloff and colleagues,53–57 has been used widely to image and quantify glucose metabolic rates in the brain, heart,44 and other organ systems, as well as to detect and map the distribution of cancer deposits in the body. FDG, like glucose, is transported from plasma into tissues via carrier-facilitated diffusion and is then phosphorylated to FDG-6-PO4 by hexokinase (the same enzyme that catalyzes the phosphorylation of glucose to glucose-6-PO4). However, FDG-6-PO4 does not serve as a substrate for further metabolism, and it does not diffuse across cell membranes. Therefore, clinical PET FDG images, usually acquired about 1 hour after intravenous administration of the compound, actually delineate closely the tissue distribution of glucose-6-PO4 as a metabolite of exogenous glucose. Mathematical modeling techniques make it possible to measure the rate of glucose metabolism using PET FDG images coupled with measurements of plasma F-18 and glucose concentrations (see references 53–57 for details). While rigorous quantification of glucose metabolism (or other physiologic or biochemical processes) with PET requires careful attention to the biochemical assumptions and the mathematical imaging methods employed,57,58 PET FDG images are proving to be useful for cancer detection and mapping because the pattern of uptake of FDG on images correlates directly with local glucose (glycolytic) metabolic rates.

Brain Tumors

Di Chiro and his colleagues59,60 were the first to use the PET FDG method in a clinical oncologic environment. They found that elevated uptakes of FDG in astrocytomas were related directly to the histology of these lesions (grade III and IV astrocytomas have higher glucose metabolic rates than grade I and II lesions), and that the method can distinguish reliably between radiation necrosis of the brain and tumor recurrences in treated patients. Since FDG uptake requires the presence of hexokinase, PET FDG localization indicates where active metabolism is occurring. Vascular contrast enhancement on CT or MRI images of the brain indicates the presence of increased permeability through the blood–brain barrier, but it does not necessarily indicate that the tissue is viable.

Since the original work by Di Chiro et al.59,60 many other investigators have demonstrated that PET FDG imaging is useful for characterizing the biochemical activity of brain tumors and for detecting tumor recurrences (Fig. 30H.1). Recent studies have also indicated that glucose consumption (as indicated by FDG uptake) is astrocytomas correlates with tumor cell density, and it is by this means that FDG uptake correlates with histologic grade. Other metabolic signals, such as elevated choline levels in local brain regions, measured by magnetic resonance spectroscopy (MRS) can also signify viable tumor as opposed to encephalomalacia.61,62 Investigations to compare the relative utility and the possible complementarity of PET and MRS for brain tumor characterization are currently in progress.63,64

Figure 30H.1. High grade astrocytoma: registered MRI and PET images.

Figure 30H.1

High grade astrocytoma: registered MRI and PET images. Contrast-enhanced spin echo T1 MRI (upper left), registered PET FDG (upper right), and two T2-weighted MRI images (less T2-weighting Te = 30 ms, TR = 2,500 ms [lower left]; more T2-weighting [Te = (more...)

Head and Neck and Other Tumors

Outside the central nervous system, other tumors that have been studied with FDG include those of the head and neck, lung, breast, colon, pancreas, musculoskeletal system, and ovary, as well as disseminated tumors, such as metastatic melanoma and the lymphomas.50

The resolution of modern PET systems makes it possible to use PET FDG imaging to detect relatively small lesions. For example, Jabour et al.65 reported a series of 12 patients with primary squamous cell carcinomas of the head and neck in which all the primary lesions were identified (CT and MRI missed one), and metastatic disease was detected in one lymph node that was anatomically normal by MRI criteria. Because of the structural complexity of the had and neck region, both the anatomic precision of MRI and the biochemical information yielded by PET can be helpful in staging cancers, particularly in identifying lymph node metastases. Following treatment (surgery and/or radiation therapy), PET FDG imaging can also help detect residual or recurrent disease, even when MRI scans are equivocal.66

While PET FDG imaging can be useful in detecting subclinical tumor deposits and depicting their distribution throughout the body using whole-body PET imaging methods,50 it is also important to remember that glucose utilization is ubiquitous in the body. Accordingly, normal glucose utilization patterns and other (nonmalignant) causes of elevated local tissue glucose utilization rates must also be considered when interpreting PET FDG images.

For example, tissue inflammation can lead to increased glucose utilization rates and increased FDG uptake on PET images.67 Nonmalignant reactive changes in lymph nodes may also produce increased FDG uptake on PET images68 in patients with cancer. Because of the quantitative precision of PET, it may be possible eventually to differentiate benign from malignant levels of glucose utilization.69 Additional clinical experience and controlled studies are needed, however, to define the specificity of various numerical thresholds for differentiating benign from malignant disease. In addition to quantitative methods, the localizing information provided by PET images and the appropriate use of clinical data in context will often facilitate the correct interpretation of PET scans.

Breast Cancer

Breast cancer is another focus of current research on PET FDG imaging.70,71 While mammography is an excellent screening tool, it may be falsely negative in up to 10% of women with cancer because of radiographically dense breast tissue. Moreover, mammography and other imaging methods, including MRI, cannot detect lymph node involvement accurately. Studies have shown that PET FDG imaging can detect primary breast lesions, as well as axillary and other metastases, in some patients, when studies with other imaging modalities have been normal.72–74

At this time, it appears that the most likely clinical role for PET in breast cancer will be in staging the disease. Because many, if not most, women currently have axillary dissections for staging purposes, staging with PET could potentially spare some women this invasive procedure. Initial results in smaller series of patients have already been promising.

Investigators at Washington University have developed a fluorinated form of estrogen [16α-F[18]fluoroestradiol-17β (FES)] and have shown that it is possible to estimate estrogen receptor density noninvasively with PET FES imaging. This form of receptor-targeted imaging also suggests another potential application of radionuclide methods in breast cancer management: combinations of FDG and FES imaging in breast cancer patients may yield insights into which patients may benefit most from antiestrogen therapy with tamoxifen.75,76

Lung Cancer

Another tumor type for which a significant amount of clinical experience with PET has accumulated is lung cancer. Benign nodules can be distinguished from malignant ones on the basis of FDG uptake, and PET with FDG has also contributed to accurate staging of mediastinal involvement in patients who have undergone combined CT and PET FDG imaging. The best results have been obtained by registering (matching with the use of computer methods) the CT and PET FDG images, so that individual lymph nodes and other structures shown on CT can be characterized biochemically with PET FDG.77

In addition to FDG studies, initial evaluations of cancer patients with other agents listed in Table 30H.1 will illustrate that the field of biochemical characterization of cancers with in vivo imaging methods is currently in its initial phase. Beyond the biochemically based approaches with PET, such as measuring glucose utilization, receptor-targeted methods promise to further facilitate detection, staging, and treatment monitoring. As an example, the hypoxic cell marker F-18 fluoromisonidazole now makes it possible to image viable but hypoxic cells. This method is not only capable of yielding insights into mechanisms of radioresistance in different tumors on the basis of hypoxic cell fractions, but it may also become a useful predictor of treatment responsiveness in individual patients.

Conclusion

Radionuclide evaluations in cancer medicine remain a mix of standard, but still evolving, techniques that are based on gamma camera methods for whole-body tumor surveys and new methods that are being driven by striking advances in radiochemistry and instrumentation. The future should see continued growth in quantitative receptor-targeted imaging approaches with SPECT and PET that will facilitate cancer detection, staging, and treatment monitoring.78–81

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