Biodistribution of indium-111-labeled OC 125 monoclonal antibody after intraperitoneal injection in nude mice intraperitoneally grafted with ovarian carcinoma.

The purpose of this work was to study the biodistribution of 111In-labeled OC 125 monoclonal antibody (MAb) with known affinity for ovarian carcinomas in a nude mouse model grafted i.p. with a human ovarian cancer (NIH:OVCAR-3). Tumor uptake 24 h after i.p. injection was higher with intact 111In-labeled OC 125 MAb (28 +/- 7.44%ID/g) than with 111In-nonspecific immunoglobulin (6.86 +/- 1.35%ID/g). The kinetics of tumor uptake also differed, showing a plateau followed by a drop at Day 7 with 111In-OC 125 MAb and a decrease beginning at 24 h with 111In-nonspecific immunoglobulin. Tumor-to-normal tissue ratios ranged between 29.91 +/- 11.85 and 0.68 +/- 0.15 with 111In-OC 125 MAb and between 4.50 +/- 1.06 and 0.53 +/- 0.04 with 111In-nonspecific immunoglobulin according to the normal tissues and the time points considered. Tumor uptake 2 h after injection was the same for F(ab')2 fragments as for intact MAb, whereas maximum uptake at 24 h (18.76 +/- 4.62%ID/g) was lower and was followed by a decrease at Day 4. Tumor-to-normal tissue ratios were in the same range, except for the tumor to blood ratio which was higher and the tumor to kidney ratio which was lower at 24 and 96 h. Maximum tumor uptake was higher after i.p. (30.77 +/- 4.76%ID/g) than i.v. (14.59 +/- 2.70%ID/g) injection. Instead of attaining the plateau noted after i.p. injection, tumor uptake after i.v. injection remained low at 2 h (2.11 +/- 1.66%ID/g), reaching its peak only after 96 h. 131I-OC 125 injected i.p., which reached maximum tumor uptake at 2 h (13.53 +/- 4.25%ID/g), showed tumor-to-tissue ratios ranging between 15.98 +/- 2.63 and 0.96 +/- 0.86, i.e., not very different from those with 111In. After i.p. injection of a radiolabeled colloid solution, maximum tumor uptake was reached at 96 h (20.22 +/- 5.35%ID/g), but with very high nonspecific uptake in liver (31.06 +/- 6.22%ID/g) and spleen (55.23 +/- 14.11%ID/g). These results indicate high, selective tumor uptake of 111In-OC 125 after i.p. injection and demonstrate the feasibility of i.p. radioimmunotherapy of ovarian carcinomas.

Biodistribution of indium-111-labeled OC 125 monoclonal antibody intraperitoneally injected into patients operated on for ovarian carcinomas.

The biodistribution of 111In-labeled monoclonal antibody (MAb) OC 125 was studied after i.p. injection in 28 patients who underwent surgery for ovarian carcinoma. Group I (eight patients) received intact 111In-labeled OC 125 MAb, Group II (three patients) intact 111In-labeled irrelevant NS, Group III (five patients) intact 111In-labeled OC 125 MAb associated with 20 mg of the same unlabeled MAb and Group IV (12 patients) F(ab')2 fragments of 111In-labeled OC 125 MAb. The patients were operated on 1 to 3 days after i.p. injection, and the surgeon removed large tumor fragments and/or small tumor nodules and, in some patients, collected the residual perfusion fluid from which malignant cell clusters were isolated. Uptake by large tumor fragments at 24 h was low: 0.0031 +/- 0.0032% injected dose per gram (%ID/g) for Group I and 0.0024 +/- 0.0022%ID/g for Group IV. It was moderately higher than that of Group II (0.0014 +/- 0.0006%ID/g) and Group III (0.0015 +/- 0.0007%ID/g). Uptake by small tumor nodules (0.1302 +/- 0.0802%ID/g at 72 h for Group I) and malignant cell clusters (median: 0.3322, with a maximum value of 4.1614%ID/g at 24 h for Group IV) was markedly higher. Tumor-to-normal tissue ratios with OC 125 MAb [intact or F(ab')2 fragments] ranged between 0.1 and 8.5 for large tumor fragments and 2 and 8,700 for small tumor nodules and malignant cell clusters. It would thus appear that RIT is feasible if an appropriate radionuclide can be selected for antibody labeling.

Positive anticalcitonin immunoscintigraphy in patients with medullary thyroid carcinoma.

A cocktail of three monoclonal F(ab')2 fragments against three distinct epitopes of calcitonin or PDN 21 was labelled with either 111In or 131I. These F(ab')2 fragments, a control 125I-F(ab')2 fragment and 99mTc-pertechnetate were injected into four patients suffering from medullary thyroid carcinoma. Scintigraphy data were processed by energy factor analysis for an optimal separation of images corresponding to each isotope. The best tumor detection was obtained 1-3 days after injection of the 111In-F(ab')2 cocktail which clearly labeled the thyroid tumors in the four patients (smallest tumor detected, 0.6 cm) as well as lymph node and bone metastases. In the liver, positive detection was only successful with the 131I-labeled cocktail. These results were confirmed by counting rates of resected specimens which provided average specificity indices ranging from 3.3 to 13.1. Anticalcitonin antibodies could be particularly useful for immunoscintigraphy detection of residual or recurrent medullary thyroid carcinoma in patients with elevated calcitonin serum level.

Imaging of myocardial infarction in dogs and humans using monoclonal antibodies specific for human myosin heavy chains.

The use of three different monoclonal antibodies specific for human ventricular myosin heavy chains in the visualization of the location and extent of necrosis in dogs with experimental acute myocardial infarction and in humans is described. Using a classic immunohistochemical method or ex vivo analysis of heart slices in dogs with acute myocardial infarction subjected to intravenous injection of unlabeled antimyosin antibodies or antimyosin antibodies labeled with indium-111, it was observed that all antibody fragments specifically reached the targeted necrotic zone less than 2 h after antibody injection and remained bound for up to 24 h. In a limited but significant number of cases (5 of the 12 humans and 11 of 43 dogs), it was possible to image the necrotic zone in vivo as early as 2 to 4 h after antibody injection. In other cases, individual blood clearance variations retarded or even prevented in vivo necrosis detection. Higher antimyosin fixation values were obtained in the necrotic zones in dogs with a rapid blood clearance relative to that of the other dogs. It is concluded that antimyosin antibodies always reached necrotic areas within 2 h. If blood clearance was rapid, in vivo imaging of the necrotic area was possible 2 to 6 h after necrosis, even in humans. In some cases, however, uncontrolled individual variations in the timing required for sufficient blood clearance hampered this rapid in vivo detection of myocardial necrosis.

Immunoscintigraphy using 111In-labeled F(ab')2 fragments of anticarcinoembryonic antigen monoclonal antibody for detecting recurrences of medullary thyroid carcinoma.

The only current possibility for curing medullary thyroid carcinoma (MTC), especially recurrences, is total surgical removal. Early positive diagnosis of recurrences is now possible by monitoring tumor markers such as thyrocalcitonin and carcinoembryonic antigen (CEA). However, preoperative topographic diagnosis of such recurrences remains an unresolved problem. Immunoscintigraphy (IS) using an anti-CEA monoclonal antibody is a new approach that complements morphological imaging, i.e. ultrasonography, computerized tomography, and magnetic resonance imaging. In this study, IS by means of an 111In-labeled anti-CEA monoclonal antibody F(ab')2 was performed nine times in eight patients. True positives were obtained five times (one case of cervical involvement confirmed by surgery, three cases of mediastinal involvement confirmed by computerized tomography, magnetic resonance imaging, and surgery, and one case of bone metastasis, one of them was revealed neither by x-ray nor by conventional bone scan). The remaining four tests gave a false positive, a true negative, a probably false negative, and one unconclusive result. We conclude that IS is helpful in diagnosing sites of MTC recurrence and should accompany other examinations in the evaluation of lesions.

Immunoscintigraphy using 111in-labelled F(ab')2 fragments of anti-carcinoembryonic antigen (CEA) monoclonal antibody for staging of non-small cell lung carcinoma.

28 patients with primitive lung cancers were imaged by immunoscintigraphy (IS) with 111indium-labelled F(ab')2 anti-carcinoembryonic antigen (CEA), to assess this technique for mediastinal staging. IS revealed primitive tumours in 21 cases in whom mediastinal extension was assessed. There was concordance between clinical staging and IS confirmed by surgery in 17 cases, and discordance in 4. After surgery, discordance was in favour of IS in 2 cases (1 true positive and 1 true negative) and in favour of clinical staging in 2 (false positive of immunoscintigraphy). Anti-CEA IS could be useful for improving mediastinal staging of lung cancer.

Immunoscintigraphy of Hodgkin's disease: in vivo use of radiolabelled monoclonal antibodies derived from Hodgkin cell lines.

The Hodgkin associated monoclonal antibody (Mab) HRS-1 reacts with Hodgkin and Reed-Sternberg cells (HR-S) in all HD subtypes. HRS-1 Mab was labelled with radioiodine and injected into 10 patients for immunoscintigraphy (IS). Seven patients were injected with HRS-1 Mab radiolabelled with 131I and three patients were injected with HRS-1 Mab labelled with 123I. A control anti-alpha-fetoprotein (anti-AFP) Mab was radiolabelled with another iodine isotope and was injected simultaneously in five cases. Six out of eight patients with proven HD had a true positive scan (nodal, splenic and bony involvement). Imaging was equivocal or failed in the two other patients. In the last two patients IS imaging was truly negative due to the absence of residual HD in one patient and to an erroneous histological diagnosis of HD in another patient. These results, although preliminary, demonstrate that IS with radioiodine-labelled HRS-1 Mab is feasible and may prove to be informative in the staging of HD.

Potential contribution of 131I-labelled monoclonal anti-CEA antibodies in the treatment of liver metastases from colorectal carcinomas: pretherapeutic study with dose recovery in resected tissues.

20 patients with liver metastases from colorectal carcinoma undergoing laparotomy received 15-60 mg intravenously, either intact or fragments of, anti-carcinoembryonic antigen (anti-CEA) monoclonal antibodies labelled with 0.55-1.48 GBq (15-40 mCi) of 131I, 3-8 days prior to operation. The uptake measured per gram of metastases ranged from 0.33 to 6.6 x 10(-3%) of injected dose. Tumour to liver uptake ratios ranged from 2 to 33. The radiation dose, estimated in 6 patients (3 of each group), for an extrapolated dose of 3.7 GBq (100 mCi) of 131I ranged from 0.3 to 0.8 Gy in normal liver or spleen (an acceptable estimate for bone marrow radiation dose) and from 3.4 to 8.2 Gy to the hepatic metastases, indicating that probably other therapeutic modalities should be associated with radioimmunotherapy.

Immunoscintigraphy of recurrences of gynecologic carcinomas.

In a first, retrospective study, 15 patients with known ovarian carcinoma were injected with 131I-OC 125 F(ab')2 monoclonal antibody (MAb). The sensitivity of immunoscintigraphy based on the number of the tumor sites was 67% (12/18). In a second, prospective study, 29 patients with gynecologic carcinoma were injected with 131I-OC 125 F(ab')2 (24) or 131I-19-9 F(ab')2 (5) MAbs according to the histologic type. Based on the number of tested anatomic sites, sensitivity was 72% and specificity 86%. In two patients injected with both 131I-OC-125 F(ab')2 and 125I-NS F(ab')2 (nonspecific immunoglobulin) 1 and 4 days before tumor resection, tumor uptake of the specific antibody was 2.2 and 4.5 times greater than that of NS. Immunoscintigraphic results were complementary with those of ultrasonography and computed tomography. Finally, in one patient injected successively with 131I-OC 125 F(ab')2 and 111In-DTPA-OC 125 F(ab')2, the recurrent tumor was visualized with both radionuclides, with 111In providing better abdominal tumor contrast but causing much greater liver radioactivity than 131I.

Immunoscintigraphy of colon carcinoma.

Two I-131 labeled monoclonal antibodies that react specifically with human gastrointestinal cancers in cell cultures were administered to 90 cancer patients for the scintigraphic detection of cancer sites. Antibody 17-1A, or its F(ab')2 fragments, accumulated significantly in 27 of 46 (59%) colorectal cancer sites, but not in 21 nonepitheliomatous colon cancers and cancers at other sites. Antibody 19-9, or its F(ab')2 fragments, showed significant accumulation in 19 out of 29 (66%) colorectal cancer sites. In 17 patients, immunoscintigraphy with antibody 19-9 correlated with an immunoperoxidase study with the same antibody on resected tissue specimens. In 12 patients injected with two antibodies (17-1A + 19-9, or anti-CEA + 19-9), ten of 13 colorectal cancer sites were positive.

Magnetic resonance imaging studies on nude mice grafted with colorectal adenocarcinoma using gadolinium-labeled monoclonal antibody.

A monoclonal antibody (Ab) 19.9 specific for colorectal carcinoma was labeled with a high number of gadolinium (Gd) atoms for its potential application as a contrast agent in magnetic resonance imaging (MRI). The DTPA was conjugated to 19.9 Ab via the bicyclic DTPA anhydride method (c. DTPA) using c. DTPA/Ab molar ratios between 5 and 150. The aggregates present in great amount at high c. DTPA/Ab ratios were systematically removed. Then the exact number of DTPA effectively conjugated, the immunoreactivity of the resulting 111In-DTPA-Ab were measured. The number of DTPA conjugated per antibody can be increased 20 to 25 with only a little loss of immunoreactivity. The 19.9 antibody conjugated with 16 and 25 DTPA was labeled with 153GdCl3 for pharmacokinetic studies on xenografted nude mice and with nonradioactive gadolinium to measure ex vivo the effect on the relaxation time T1 of the tumor. We found a 15 to 20% decrease of T1 on the tumor. In vivo experiments using a Bruker system and the same animal model showed a difference in the tumor contrast after the injection of 2 mg of Gd-labeled Ab.

Radiolabeled monoclonal antibodies against Reed-Sternberg cells for in vivo imaging of Hodgkin's disease by immunoscintigraphy.

The Hodgkin Reed-Sternberg (HRS-1) monoclonal antibody (Mab) was raised against the L 428 Hodgkin's disease (HD) cell line. The HRS-1 Mab was labeled with radioactive iodine and injected into six patients with Hodgkin's disease of varied histological subtypes for immunoscintigraphic imaging. In five patients, the HRS-1 Mab was labeled with 131I; a control anti-alpha-fetoprotein (AFP) Mab was injected simultaneously in two of these five cases. Four of five patients had a positive scan (nodal, splenic and hepatic involvements), the results in the fifth patient being equivocal. In the sixth patient, the HRS-1 Mab was labeled with 123I in order to utilize tomoscintigraphy instead of linear scintigraphy. Although the immunoscintigraphy (IS) was performed secondary to effective chemotherapy, images of bony disease were demonstrated. These preliminary results demonstrate that IS with iodine-labeled HRS-1 Mab is feasible and informative in Hodgkin's lymphoma. The real clinical value and the specificity of IS deserves confirmation in a larger series of patients. Several techniques such as the use of Fab or F(ab')2 fragments should further improve the results.

[Influence on extratumoral organ activities of tumor-affinity samarium-153 preparations]. / Beeinflussung extratumoraler Organaktivitäten von tumoraffinen Samarium-153-Zubereitungen.

AIM: Possibilities to exercise an influence on the biodistribution of a tumor-affine 153Sm-preparation, samarium-153-nitrilotriacetate (NTA), were tested. METHODS: Animals experiments on tumor-bearing mice after additional application of EDTMP (ethylenediamine tetramethylene phosphonate) for the reduction of extratumorale liver-radioactivity and yttrium chloride for the reduction of unwanted underground radioactivity in bone were carried out. Furthermore, the combination of both measurements was tested. RESULTS: The biodistribution of 153Sm-NTA showed a rather low tumor-radioactivity of app. 0.72%/g. The additional EDTMP-application caused a dose-dependent decrease of the underground-radioactivity in liver especially if given 2 h in advance or simultaneously. The additional application of the stable yttrium salt reduced the bone radioactivity on simultaneous increase of liver- and spleen-radioactivity and practically unchanged tumor-radioactivity. The combined use of EDTMP together with the bone-affine metal salt led to a reduction of liver radioactivity on simultaneous reduction of bone radioactivity. CONCLUSIONS: The background radioactivity can be reduced on unchanged tumor-radioactivity by combined Na-EDTMP/YCl3-application. The present results do not allow a therapeutic exploitation because of the low tumor accumulation.

[Immunoscintigraphy and radioimmunotherapy of transplanted pancreatic carcinoma. Experimental animal studies with 131I-labeled monoclonal antibodies against CA 19-9, CEA and CA 125]. / Immunszintigraphie und Radioimmuntherapie des transplantierten Pankreaskarzinoms. Tierexperimentelle Untersuchungen mit 131J-markierten monoklonalen Antikörpern gegen CA 19-9, CEA und CA 125.

The immunoscintigraphic results in 12 human pancreatic carcinomas established on nude mice (Nu-Nu-Balb-C) are reported. The transplanted tumors corresponded to the human cancers concerning histology, grading, immunohistochemistry and secretion of tumor-associated antigens. 131I-labeled monoclonal antibodies against CA 19-9, CEA and CA 125 were used. These antigens are found in the serum of more than 90% of patients with pancreatic carcinoma at the time of first diagnosis. The result show that pancreatic carcinomas are detectable with the antibodies applied here. The quality of the scintigraphic detection depends, among other factors, on the antibody affinity to the tumor, the localization and the size of the tumor. Preliminary results of the studies on radioimmunotherapy of pancreatic cancer with 131I-anti-CA 19-9 indicate that effective absorbed doses in the tumor may be achieved via intravenous application only in cases with a rather high expression of the tumor antigen. But direct instillation into the tumor enables therapeutic radiation doses to the tumor even with moderate affinity and a low whole-body burden, as shown by experiments in 8 mice bearing 4 different human pancreatic carcinomas, 3 with positive and 1 with negative affinity to CA 19-9: the tumor retentions and the effective half-lives of 131I-anti-CA 19-9 were measured after intratumoral (100 microCi/mg tumor) or intravenous (30 and 190 microCi/g body weight) application.

[Immunotargeting of tumors: state of the art and prospects in 2000]. / Immunociblage des tumeurs: situation et perspectives en 2000.

Following 15 years of experimental studies, tumor immunotargeting using monoclonal antibodies directed against tumor associated antigens shows now important monoclonal antibodies directed against tumor associated antigens shows now important clinical developments. This is mainly due to encouraging therapeutic results which have obtained using humanized antibodies such as the anti-CD20 rituximab in follicular B lymphomas and the anti-DrbB2 herceptin in breast carcinomas. Thanks to genetic engineering it is possible to graft variable or hypervariable regions from murine antibodies to human IgG, and even to obtain fully human antibodies by using either transgenic mice containing a large part of the human repertoire of human IgG, or selection of human antibody fragments expressed by phages. Radiolabeling of antibodies played a major role to demonstrate the tumor immunotargeting specificity and remains attractive for the diagnosis by immunoscintigraphy as well as for the treatment by radioimmunotherapy of some cancers. In this review, the current results and the prospects of diagnostic and therapeutic uses of anti-tumor antibodies and their fragments will be described. Concerning diagnosis, 123-iodine or 99m-technetium labeled Fab fragments allowed very demonstrative tumor images but this technique has a limited effect upon the therapeutic attitude. Immuno-PET (positron emission tomography) could enhance the sensitivity of this imaging method. Radio-immunoguided surgery and immunophotodetection are attractive techniques still under evaluation. Concerning therapy, 131-iodine labeled anti-CD20 antibodies gave spectacular results in non-Hodgkin's B lymphomas. In solid tumors which as less radiosensitive, radioimmunotherapy could concern small tumors and need the use of two-steps targeting and/or alpha emitters radioisotopes. Some other strategies will be described such as bispecific antibodies directed against tumors and immune effector cells, some antibody fragments expressed on T cells called T-bodies or some biological studies using intrabodies. Published data and works in progress demonstrate that immunotargeting of tumors will have a growing place in the treatments of cancer patients.

Direct 99mTc labeling of monoclonal antibodies: radiolabeling and in vitro stability.

Direct labeling involves 99mTc binding to different donor groups on the protein, giving multiple binding sites of various affinities resulting in an in vivo instability. The stability has been considerably improved by activating the antibody using a controlled reduction reaction (using 2-aminoethanethiol). This reaction generates sulfhydryl groups, which are known to strongly bind 99mTc. The direct 99mTc antibody labeling method was explored using whole antibodies and fragments. Analytical methods were developed for routine evaluation of radiolabeling yield and in vitro stability. Stable direct antibody labeling with 99mTc requires the generation of sulfhydryl groups, which show high affinity binding sites for 99mTc. Such groups are obtained with 2-aminoethanethiol (AET), which induces the reduction of the intrachain or interchain disulfide bond, with no structural deterioration or any loss of immunobiological activity of the antibody. The development of fast, reliable analytical methods has made possible the qualitative and quantitative assessment of technetium species generated by the radiolabeling process. Labeling stability is determined by competition of the 99mTc-antibody bond with three ligands, Chelex 100 (a metal chelate-type resin), free DTPA solution and 1% HSA solution. Very good 99mTc-antibody stability is obtained with activated IgG (IgGa) and Fab' fragment, which makes these substances possible candidates for immunoscintigraphy use.

Gd-25 DTPA-MAb, a potential NMR contrast agent for MRI in the xenografted nude mouse: preliminary studies.

Monoclonal antibodies (MAbs) 19-9 and 73-3 specific for human colon adenocarcinoma were labelled with a high number of gadolinium atoms. Twenty five DTPA were chelated per MAb, with only slight loss of immunoreactivity. The NMR contrast agent Gd-25 DTPA-MAb 19-9 or 73-3 ([Gd] 17 mumole/kg, [MAb] 60 microM) was injected into nude mice bearing human colon adenocarcinoma (SW948). Tumours were removed 24 hr after injection and T1 was measured in vitro. T1 relaxation time varied according to MAb specificity against tumour targets; T1 decreased 20% for MAb 19-9 and MAb 73-3 with SW948 tumour. Imaging was performed with this model. Very good contrast was obtained 24 hr after Gd-25 DTPA-MAb injection.

Pharmacokinetic study of radiolabeled anti-colorectal carcinoma monoclonal antibodies in tumor-bearing nude mice.

Monoclonal antibodies (MoAbs) 17-1A and 19-9, which specifically bind human colorectal carcinoma (CRC) cells, were tested for their usefulness in localizing colorectal tumors in nude mice. One of the 131I-labeled MoAbs and an irrelevant 125I-labeled immunoglobulin of the same isotype were injected into nude mice simultaneously bearing a human CRC and a human melanoma. The percentage of the injected dose of antibody per gram of tissue, the CRC/tissue ratios of antibody distribution, and the localization indices were calculated at various time intervals (2 h to 9 days). For both MoAbs, labeling to a specific activity of 10 microCi/microgram by the iodogen method gave optimum immunoreactivity. The accumulation of MoAb 17-1A in CRC reached is maximum at 5 days and remained at this level for up to 9 days postinjection. For MoAb 19-9, which detects a circulating antigen shed by the tumor into the serum, the accumulation in the CRC was maximum at 24 h, and decreased thereafter. The CRC/organ ratios and localization indices for both MoAbs increased with time in the CRC tissue, but remained low and unchanged in the melanoma and normal tissues. Using F(ab')2 antibody fragments, faster kinetics with earlier maximum accumulation, higher tumor/organ ratios, and better localization indices were achieved than with intact MoAbs. The data obtained was useful in defining parameters which must be considered before radiolabeled MoAbs are used in cancer patients for diagnostic purposes.

Radioimmunodetection of lymph node invasion in prostatic cancer. The use of iodine 123 (123I)-labeled monoclonal anti-prostatic acid phosphatase (PAP) 227 A F(ab')2 antibody fragments in vivo.

The therapeutic indications in prostatic cancer depend on the regional and distant extension of the cancer and are difficult to assess before lymphadenectomy. Radioimmunodetection of lymph node involvement with monoclonal anti-prostatic acid phosphatase (PAP) antibodies can be proposed as a noninvasive alternative to lymphadenectomy. Fifteen patients with various stages of histologically proven prostatic cancer were examined by immunolymphoscintigraphy (ILS) before treatment to detect lymph node metastases. These patients had Stage A (n = 7), Stage B (n = 3), Stage C (n = 2), and Stage D (n = 3) tumors. They received between 100 and 400 micrograms of monoclonal antibody 227 A in the form of F(ab')2 fragments labeled with iodine 123 (123I). The antibody was injected directly into the periprostatic area. ILS images were obtained after 1, 3, 6, and 24 hours. Three days later, each patient underwent a lymphadenectomy for histologic examination. The results of the histologic examination and ILS were compared. In ten patients, the examination did not show any images capable of being interpreted as lymphadenopathy and histologic examination confirmed the integrity of the nodes examined. In five cases, scintigraphy suggested the presence of lymph node invasion by prostatic cancer and this was confirmed by histologic examination in three of the five cases. Overall, in terms of lymphadenopathy, this examination had a sensitivity of 100% and a specificity of 83%. Therefore, ILS appears to be capable of detecting lymph node metastases in prostatic cancer.