A prospective study of factors predicting clinically occult spinal cord compression in patients with metastatic prostate carcinoma.

BACKGROUND: The objective of this study was to identify clinical parameters that predict occult subarachnoid space or spinal cord (SAS/SC) compression, as determined by magnetic resonance imaging (MRI), in patients with metastatic prostate carcinoma. METHODS: A prospective study was performed in which 68 patients with bone metastases from prostate carcinoma and a normal neurologic examination underwent MRI of the entire spine after documentation of clinical, X-ray, and bone scan parameters potentially predictive of occult SAS/SC compression. RESULTS: Occult SAS/SC compression was diagnosed in 22 patients (32%) using MRI. Nine patients (13%) had compressions at two discontinuous spinal levels. Extensive disease on bone scan, the duration of continuous hormonal therapy prior to study entry, and hemoglobin concentration were found to predict SAS/SC compression by univariate analysis. The extent of disease on bone scan and the duration of continuous hormonal therapy were independent predictors of SAS/SC compression by multivariate analysis (P = 0.02 and P = 0.04, respectively). The risk of occult SAS/SC compression increased from 32% to 44% in patients with a bone scan that showed > 20 metastases as the duration on hormones increased from 0 to 24 months. The risk in patients with fewer metastases increased from 11% to 17% over the same interval. The presence or absence of back pain was not predictive of SAS/SC compression. CONCLUSIONS: Patients who are at high risk for occult SAS/SC compression can be identified using clinical parameters and readily available diagnostic tests. These high-risk patients should undergo MRI screening with the aim of diagnosing and treating spinal cord compression before the development of neurologic deficits that may be irreversible.

Sentinel node detection and definition may depend on the imaging agent and timing.

PURPOSE: Two cases of sentinel lymph node imaging are presented in which the results are exceptions to what the literature generally defines as sentinel lymph nodes. In one case, Tc-99m antimony trisulfide colloid produced significantly different results than did Tc-99m tin colloid. In the second case, the results bring into question the definition of a sentinel node as the first in a lymphatic drainage pathway. MATERIALS AND METHODS: In one patient, lymphoscintigraphy was performed initially using Tc-99m antimony trisulfide colloid injected intradermally around a melanoma excision site. Repeated lymphoscintigraphy 1 month later, 1 hour before sentinel node excision, was done using Tc-99m tin colloid, a larger particle than antimony trisulfide colloid. The second patient, with a melanoma biopsied only, had sentinel node imaging performed using Tc-99m sulfide colloid, a particulate also larger than antimony trisulfide colloid and also 1 hour before sentinel node excision. RESULTS: In the first patient, imaging with the smaller antimony trisulfide colloid showed more lymphatic pathways and more sentinel nodes than with tin colloid. In the second patient, the first focus of retention of the imaging agent in the lymphatic pathway seen showed less intense accumulation than the next focus in the pathway, contrary to published reports that the sentinel node shows more intense accumulation than do nodes further downstream in a lymphatic pathway. CONCLUSIONS: There are exceptions to published characteristics of sentinel node lymphoscintigraphy, so care must be exercised in localizing sentinel nodes.

Simulation of renal function by tumor and its effect on the calculated glomerular filtration rate.

A patient with a retroperitoneal sarcoma near the left kidney was to undergo radiotherapy. Renal assessment with Tc-99m DTPA to determine renal function before radiotherapy resulted in what was thought to be a low glomerular filtration rate based on the Gates computer method and the Russell two-blood-sample method. Most likely this resulted from the observed significant accumulation of DTPA in the tumor for the first few minutes with washout for the rest of the imaging time, simulating renal function.

Gallium accumulation in marrow lymphocytes.

A case of Ga-67 and Tc-99m WBC imaging in a patient is shown in which the discrepancy in the accumulation of the two imaging agents in radiated bone indicates that gallium accumulated predominantly in marrow lymphocytes in the skeleton of this patient.

Technetium-99m-tetrofosmin as a substrate for P-glycoprotein: in vitro studies in multidrug-resistant breast tumor cells.

UNLABELLED: The accumulation of 99mTc-tetrofosmin (TFos) was studied in wildtype (WT) and doxorubicin-resistant (AdrR) variants of the rat MatB and human MCF-7 breast tumor cell lines to determine whether TFos, like 99mTc-sestamibi (MIBI), is a substrate for P-glycoprotein (P-gp), a multidrug-resistance transporter. METHODS: The time course of accumulation of TFos and MIBI in WT and AdrR cells over 1 hr was studied using single-cell suspensions at 1 x 10(6) cells/ml incubated at 37 degrees C in the presence or absence of PSC833, a potent modulator of P-gp. Modulator dose-response curves were generated for PSC833, cyclosporin A, and verapamil. RESULTS: In both MatB and MCF-7 cells, TFos and MIBI accumulated extensively in WT cells and accumulation was not affected by PSC833. In contrast, ADrR cell lines accumulated very little of either tracer, but addition of PSC833 or other modulator increased this accumulation in a dose-dependent fashion. TFos and MIBI did not differ significantly in their behavior. CONCLUSION: TFos shares with MIBI the property of being a substrate for P-gp and thus TFos may be useful for functional imaging of tumor P-gp status.

Imaging inflammation with 99Tcm-labeled chemotactic peptides: analogues with reduced neutropenia.

Two 99Tcm-labelled analogues of the chemotactic peptide ForMLF were evaluated as potential agents for imaging inflammation and infection, in the hope that they would be simple to use and would give diagnostically useful images shortly after injection. The peptides differed in the chelation site for 99Tcm and the presence of a hydrophilic spacer. The sequences of RP050 and RP056 were ForNleLFNleYK(G)G-C(Acm)-GPic and ForNleLFNleYKK(DG)GC(Acm)SPic respectively, where Pic is picolinic acid. In in vitro tests of binding to the ForMLF receptor on polymorphonuclear neutrophils and potency for release of myeloperoxidase, RP056 was similar in potency to ForMLF, whereas RP050 was 10 times more potent. When administered in 5-nmol doses to rats, RP050 produced less extensive neutropenia than ForMLF, whereas RP056 produced very little neutropenia. Following labelling by ligand exchange from tartrate or glucoheptonate at 100 degrees C and purification using a C-18 solid-phase extraction cartridge, 4-MBq doses were administered to rats bearing infectious (Escherichia coli) or sterile (zymosan) inflammation sites in the thigh. The inflammation-to-normal muscle ratios at 30 min after injection were 3.9 +/- 0.4 for RP050 and 4.7 +/- 0.3 for RP056 (mean +/- S.E.M., n = 4), and the ratios were maintained for up to 3 h. These peptides are promising agents for imaging inflammation and infection.

Differences between accumulation of 99mTc-MIBI and 201Tl-thallous chloride in tumour cells: role of P-glycoprotein.

Both 99mTc-MIBI and 201Tl have been used for tumour imaging. It has recently been reported that 99mTc-MIBI is a substrate for P-glycoprotein (Pgp), a membrane pump which mediates multidrug resistance. We have evaluated the role of Pgp in the cellular accumulation of 201Tl by using sensitive and resistant strains of Chinese hamster ovary (CHO) fibroblasts (AuxB1 and CHRC5, respectively) grown in suspension culture. 201Tl accumulation was the same in sensitive and resistant cells, whereas 99mTc-MIBI accumulation was much lower in resistant cells than in sensitive ones. Down-modulation of Pgp with 100 microM verapamil did not alter cellular accumulation of 201Tl while it significantly increased 99mTc-MIBI accumulation in both types of cell. Similarly, 10 microM verapamil did not affect the rate of washout of 201Tl from preloaded cells, while 99mTc-MIBI washout was greatly reduced in the presence of verapamil. These results suggest that 201Tl will accumulate in both sensitive and resistant tumour cells, whereas 99mTc-MIBI will be extruded from resistant cells and therefore may be less useful for tumour detection when the tumour cells express high Pgp levels.

Labelling small quantities of monoclonal antibodies and their F(ab')2 fragments with technetium-99m.

Addition of sulfhydryl groups with 2-iminothiolane (2-IT) is an important new method for labelling monoclonal antibodies (mAb) and fragments with 99mTc. F(ab')2 fragments were prepared by digestion of 1B7.11 and BCD-F9 with pepsin. Optimal conditions for labelling 20-100 micrograms mAb or F(ab')2 involved a 2000:1 molar ratio of 2-IT:protein in phosphate buffer pH 7.4 for 30 min followed by addition of 99mTc-pertechnetate and stannous glucoheptonate. Recovered yields were > 70% and radiochemical purities were > 90% with a total preparation time of < 90 min.

99Tcm-sestamibi as an agent for imaging P-glycoprotein-mediated multi-drug resistance: in vitro and in vivo studies in a rat breast tumour cell line and its doxorubicin-resistant variant.

Multi-drug resistance mediated by the transmembrane pump P-glycoprotein (Pgp) is an important mechanism of resistance of certain tumours against chemotherapeutic drugs. The myocardial perfusion imaging agent 99Tcm-sestamibi is a substrate for Pgp. Further characterization of 99Tcm-sestamibi has now been carried out in the transplantable rat breast adenocarcinoma cell line, MatB, and its doxorubicin-resistant variant, AdrR. In vitro accumulation of the tracer in wild-type (WT) MatB was high and was not affected by the Pgp modulator, PSC833. Conversely, AdrR cells did not accumulate significant amounts of tracer unless PSC833 was present. Imaging studies in rats bearing MatB-WT and AdrR tumours showed that 99Tcm-sestamibi washed out of the resistant tumours at three times the rate of WT tumours. These results support the potential use of 99Tcm-sestamibi for functional imaging of Pgp activity in patients undergoing chemotherapy.

Effect of hypoxia on the accumulation of technetium-99m-glucarate and technetium-99m-gluconate by Chinese hamster ovary cells in vitro.

The accumulation of 99mTc-glucarate, an agent recently reported to localize in acutely infarcted myocardium, zones of acute cerebral injury and tumors, has been compared with 99mTc-gluconate in an in vitro system of cultured Chinese hamster ovary fibroblasts. The effects on accumulation of hypoxia and competition with fructose have been studied. Both labeled glucose analogs showed a two- to threefold enhanced accumulation in hypoxic cells relative to aerobic cells. No such enhanced accumulation under hypoxia was observed for the nonsugar tracers pertechnetate and 99mTc-DTPA. The presence of 20 mM fructose reduced the accumulation of 99mTc-glucarate by 30% (p = 0.067) and 99mTc-gluconate by 40% (p < 0.05) in hypoxic cells, but had no significant effect in aerobic cells. These results suggest that both compounds at least partially share a common mechanism of uptake and/or accumulation with fructose.

Formulation of technetium-99m-aerosol colloid with improved delivery efficiency for lung ventilation imaging.

Static imaging of lung ventilation in multiple views or with SPECT requires a 99mTc aerosol which does not wash out during imaging. Commercially available 99mTc colloids have suitable physical properties but are inefficiently delivered from jet nebulizers. An in vitro system was used to compare the delivery of various 99mTc radiopharmaceuticals from nebulizer solutions. Delivery of noncolloidal agents (pertechnetate, pentetate, imidodiphosphate, albumin) was much greater than that of colloids. However, addition of phosphate buffer to an in-house 99mTc-tin colloid produced an agent that was delivered as efficiently as the noncolloidal tracers and which shows promise for clinical use.

Evaluation of reduction-mediated labelling of antibodies with technetium-99m.

Monoclonal antibodies can be labelled with technetium-99m by prereduction of the antibody with 2-mercaptoethanol, then reduction of pertechnetate with an aliquot of a stannous kit, resulting in greater than 97% labelling without the need for further purification. The present work shows that equally high labelling can be obtained with a variety of weak ligands and that the optimum quantity of stannous chloride is 2-4 micrograms. Although the label was stable to challenge with excess DTPA, cysteine was able to remove a portion of the label. We have also shown that this technique works with the IgG2a isotype in addition to the previously reported IgG1 isotype. This approach is simple, convenient and reproducible, and warrants further clinical evaluation.

Gallium-67-labelled red blood cells as a blood-pool marker for dual-isotope imaging.

Red blood cells were labelled with 67Ga oxine prepared from 67Ga citrate, a routinely available and relatively inexpensive radiopharmaceutical which is suitable for dual-isotope imaging with 99mTc. Labelling efficiency was 88 +/- 1%, 24-h in vitro stability was 93 +/- 5% in saline at room temperature and 68 +/- 4% in whole blood at 37 degrees C, and the method could be performed within 20-30 min.

Nuclear medicine detection of inflammation and infection.

The diagnosis and localization of inflammation and infection by nuclear medicine techniques continue to improve. The past year has seen a number of innovations and improvements in both commonly used radiopharmaceuticals and those still in the research phase. A good, in-depth knowledge of the many pathophysiologic changes that can occur at various sites and with different etiologies remains important in understanding and choosing which tests are most likely to provide useful clinical information. A number of important publications over the past year are reviewed.

Internal mammary lymphadenopathy: imaging of a vital lymphatic pathway in breast cancer.

The prognostic significance of metastases to the internal mammary lymph nodes in patients with breast carcinoma has long been recognized. While ipsilateral dissection of axillary nodes remains a popular staging strategy for breast cancer, surgical sampling of the upper anterior intercostal spaces, a tedious procedure, has been largely abandoned. Diagnostic imaging of the parasternal lymphatic pathway is a useful and noninvasive alternative to surgical staging. This report reviews the pertinent regional anatomy and illustrates the criteria for diagnosing internal mammary lymphadenopathy by means of lateral chest radiography, computed tomography, high-resolution sonography, magnetic resonance imaging, and radionuclide lymphoscintigraphy.

Nasal secretion of iodine-131.

A case of total-body I-131 imaging showing an abnormal collection of I-131 is presented. The site of uptake was initially thought to be a thyroid carcinoma metastasis in the upper right thigh but was subsequently shown to be due to the nasal secretion of I-131 contaminating a handkerchief. Other possible causes of I-131 contaminated handkerchiefs are also discussed.

Lymphoscintigraphy for cystic hygroma.

We present the case of an infant with a cystic hygroma investigated by lymphoscintigraphy. The source of lymph flowing into the hygroma was identified as were some ectatic lymphatics feeding it. Lymph flow was very rapid. The implications for therapy are discussed. Lymphoscintigraphy can assess many aspects of lymph flow not accessible by other means.