[Laparoscopic sentinel lymph node (SLN) dissection for clinically localized prostate carcinoma: results obtained in the first 70 patients]. / Détection laparoscopique des ganglions sentinelles dans le cancer localisé de la prostate: résultats obtenus chez 70 premiers patients.

OBJECTIVES: The lymph node metastasis is an important prognostic factor in prostatic cancer. The aim of this prospective study was to evaluate the relevance of the sentinel lymph node biopsy by laparoscopy in staging locoregional patients with clinically localized PC. PATIENTS AND METHODS: A transrectal ultrasound-guided injection by 0.3 mL/100 MBq (99m)Tc-sulfur rhenium colloid in each prostatic lobe was performed the day before surgery. The detection was realized intraoperatively with a laparoscopic probe (Clerad(®) Gamma Sup) followed by extensive dissection. Counts of SLN were performed in vivo and confirmed ex vivo. The histological analysis was performed by hematoxyline-phloxine-safran staining and followed by immunochemistry if SLN is free. RESULTS: Seventy patients with carcinoma of the prostate at intermediate or high risk of lymph node metastases were included. The intraoperative detection rate was 68/70 (97%). Fourteen patients had lymph node metastases, six only in SLN. The false negative rate was 2/14 (14%). The internal iliac region was the first metastatic site (40.9%). A metastatic sentinel node in common iliac region beyond the ureteral junction was present in 18.2%. A non-negligible sentinel metastatic region was the common iliac area (18.2%). Limited or standard lymph node dissection would have ignored respectively 72.7% and 59% of lymph node metastases. CONCLUSION: The laparoscopy is adapted to a broad identification of SLN and targeted dissection of these lymph nodes significantly limited the risk of surgical extended dissection while maintaining the accuracy of the information.

[Sentinel node detection applied to breast cancer: 2007 update]. / La détection du ganglion axillaire sentinelle appliquée au traitement du cancer du sein: le point en 2007.

The technique of detection and resection of the sentinel lymph node applied to early breast cancer management aims to spare the patient with a low risk of lymph node involvement an unnecessary axillary lymphadenectomy. This innovating technique lies on the double hypothesis of an accuracy to predict non sentinel lymph node status and to induce a lower morbidity when compared with axillary lymphadenectomy. This multidisciplinary technique depends on surgeons, nuclear physicians and pathologists. In practice sentinel lymph nodes are detected thanks to two types of tracers, the Blue and the colloids marked with technetium, harvested by the surgeon guided by the blue lymphatic channel and the use of a gamma probe detection, analyzed by the pathologist according to a particular procedure with the concept of serial slices, and possibly immuno histo chemistry. The objectives of this review are to specify the state of knowledge concerning the different steps: detection, surgical resection and the pathological analysis of the sentinels lymph nodes and to focus on validated and controversial indications, and on the main ongoing trials.

The impact of nonvisualization of sentinel nodes on lymphoscintigraphy in breast cancer.

BACKGROUND: This study aimed at evaluating the relationship between the nonvisualization of sentinel nodes (SNs) at lymphoscintigraphy and the intraoperative detection rate, radioactive counts in vivo, and histological status of SNs. METHODS: Two hundred eighty patients with infiltrating breast carcinoma (T0, T(1)/T(2)) underwent preoperative lymphoscintigraphy before gamma probe-guided SN biopsy. RESULTS: The surgical identification rate with a gamma probe was 84.6% (56 of 280) in lymphoscintigraphy-negative patients and 93.2% (224 of 280) in lymphoscintigraphy-positive patients (P < .05) after two subdermal periareolar injections. The average number of SNs per patient was 1.7 in lymphoscintigraphy-negative patients and 2.2 in lymphoscintigraphy-positive patients (P < .01), as assessed by gamma detection. The mean age of lymphoscintigraphy-negative patients was 62 +/- 10 years, versus 55 +/- 13 years for lymphoscintigraphy-positive patients (P < .001). The median radioactive count in dissected SNs identified by gamma detection was 204 cps (range, 4-618 cps) in lymphoscintigraphy-negative patients, versus 606 cps (range, 43-16,928 cps) in lymphoscintigraphy-positive patients (P < .001). The rate of macrometastatic SNs was 40% in lymphoscintigraphy-negative patients, versus 30% in lymphoscintigraphy-positive patients (not significant), whereas the size of involved SNs was 16.6 mm in lymphoscintigraphy-negative patients, versus 13.1 in lymphoscintigraphy-positive patients (P < .05). The micrometastasis detection rate in SNs from lymphoscintigraphy-negative patients was 6.25%, versus 23.3% in lymphoscintigraphy-positive patients (P < .01). CONCLUSIONS: Negative lymphoscintigraphy was observed in 20% of patients and was more frequent in elderly patients. Negative lymphoscintigraphy was predictive of a lower surgical identification rate and fewer detected SNs. These SNs had fewer micrometastases, were fairly large, and tended to harbor metastases.

Learning curve for the detection of axillary sentinel lymph node in breast cancer.

AIM: Sentinel axillary lymph node (SALN) detection is a new technique. Surgeons must progress up a learning curve in order to guarantee quality and safety equivalent to axillary lymphadenectomy. To ensure accurate staging of patients this learning curve must include SALN detection and an axillary lymphadenectomy. The aim of our work was to validate the principles and evaluate the consequences of learning curve for SALN detection from a prospective series of 200 consecutive patients. METHOD: Prospective assessment was made of the detection and false negative rates, post operative morbidity as abcess and seroma, and length of hospital stay. RESULTS: We evaluated the performance from the first to the hundredth case for each surgeon. Detection rate improved to 85% after patient number 10. False negative rate was less than 6%. Post operative axillary morbidity included 11% of seromas and 2% of abcess. Mean hospital stay was 2.8 days. CONCLUSION: Multidisciplinary validation of the learning period contributes to an accurate and safe SALN.

Lymphoscintigraphy in the sentinel lymph node technique for breast tumor: value of early and late images for the learning curve.

As the performance of early (H+1 to H+4) and late (D1) lymphoscintigraphic images raises organizational problems in outpatient surgery for breast cancer, only early images are generally obtained. The present study evaluated whether two series of images are better than one and defined the advantages of both methodologies. One hundred and eighteen patients with infiltrating breast carcinoma (T(0), T(1) and T(2)) were included in the study: 87 in group A (early and late images) and 31 in group B (only early images). All patients received two peritumoral injections of (99m)Tc-sulfur colloid, 15-18 MBq (group A) and <15 MBq (group B). During the operation, the patent blue bye technique was associated with radioactivity detection. The two groups were comparable for histological type and tumor size and localization. Successful localization of sentinel nodes on early lymphoscintigraphic images was significantly greater for group B. The identification of a sentinel node focus on early lymphoscintigraphy increased by 10% during the study. Sentinel node detection by the isotopic method alone, or the two methods combined, was comparable for both groups. In radioactivity detection, the count rate for sentinel nodes versus background (contralateral breast) was similar for the two groups. During the learning phase, two series of images gave a definite advantage. Subsequently, lymphoscintigraphy performed at +2 h was sufficient (the results for the two groups became indistinguishable).

Two-step targeting of xenografted colon carcinoma using a bispecific antibody and 188Re-labeled bivalent hapten: biodistribution and dosimetry studies.

UNLABELLED: Radioimmunotherapy (RIT) is currently being considered for the treatment of solid tumors. Although results have been encouraging for pretargeted 131I RIT with the affinity enhancement system (AES), the radionuclide used is not optimal because of its long half-life, strong gamma emission, poor specific activity, and low beta particle energy. 188Re, though unsuitable for direct antibody labeling, could be used with the AES two-step targeting technique. The purpose of this study was to compare the distribution and dosimetry of a bivalent hapten labeled with 188Re or 125I. For dosimetry calculations and biodistribution data, 125I was substituted for 131I. METHODS: After preliminary injection of a bispecific anticarcinoembryonic antigen (CEA) or antihapten antibody (Bs-mAb F6-679), AG 8.1 or AG 8.0 hapten radiolabeled with 188Re or 125I was injected into a nude mouse model grafted subcutaneously with a human colon carcinoma cell line (LS-174-T) expressing CEA. A dosimetry study was performed for each animal from the concentration of radioactivity in tumor and different tissues. RESULTS: Radiolabeling of AG 8.1 with 125I afforded a 40% yield with a specific activity of 11.1 MBq/nmol after purification. Radiolabeling of AG 8.0 with 188Re afforded a 72% yield with a specific activity of 31.82 MBq/nmol. In all experiments, the percentage of tumor uptake of 125I-AG 8.1 was always significantly greater than that of 188Re-AG 8.0. The corresponding tumor-to-tissue ratios reflected uptake values. The least favorable tumor-to-normal tissue ratios in the dosimetry study were 8.1 and 8.5 for 131I (tumor-to-blood ratio and tumor-to-kidney ratio, respectively) and 2.3 for 188Re (tumor-to-intestine ratio). CONCLUSION: This study indicates that 188Re can be used for radiolabeling of hapten in two-step radioimmunotherapy protocols with the AES technique. 188Re has a greater range than 131I, which should allow the treatment of solid tumors around 1 cm in diameter. Although the method used for hapten radiolabeling did not provide optimal tumor uptake, the use of a bifunctional chelating agent associated with AG 8.1 should solve this problem.

Polylysine-Gd-DTPAn and polylysine-Gd-DOTAn coupled to anti-CEA F(ab')2 fragments as potential immunocontrast agents. Relaxometry, biodistribution, and magnetic resonance imaging in nude mice grafted with human colorectal carcinoma.

RATIONALE AND OBJECTIVES: Immunocontrast agents used for magnetic resonance imaging require antibodies that preserve the immunoreactivity while containing a high number of chelated paramagnetic ions. METHODS: Anti-CEA F(ab')2 fragments were coupled to polylysine-Gd-DOTA and polylysine-Gd-DTPA. A paramagnetic load as high as n = 24 to 28 metal ions per antibody was reached. RESULTS: The immunoreactivity of the gadolinium (Gd)-labeled anti-CEA F(ab')2 immunoconjugates was 80% to 85%. Compared with that of commercial chelates, the relaxivity (R1) increase is as follows: Gd-DTPA < Gd-DOTA < Gd-H2O < PL-Gd-DTPA24-28 < PL-Gd-DTPA24-28 F(ab')2 < PL-Gd-DOTA24-28 < PL-Gd-DOTA24-28 F(ab')2. 1H nuclear magnetic relaxation dispersion data of immunoconjugates showed that the high relaxivity enhancement was the result of a reduction of the molecular tumbling rate. Twenty-four hours after intravenous injection of 50 micrograms (1 mumol Gd/kg) of Gd-labeled immunoconjugates to nude mice grafted with human colorectal carcinoma LS 174T, the tumor uptake was 10% to 15%, resulting in an increase of R1 of up to 15% to 20% versus noninjected mice. No difference was found between PL-Gd-DTPA24-28 F(ab')2 and PL-Gd-DOTA24-28 F(ab')2 immunoconjugates for tumor, liver, and kidney uptake. A high signal intensity of tumor was observed in 50% of the tested mice.

Angiomagnetic resonance imaging of iliofemorocaval venous thrombosis.

Although magnetic resonance imaging has been proposed for the diagnosis of deep venous thrombosis (DVT), its role in diagnostic strategy remains to be defined. We compared prospectively magnetic resonance angiography (MRA) with two-dimensional time-of-flight with contrast venography (CV) and colour duplex sonography (CDS) in 25 patients with DVT of the pelvis confirmed by CV. All patients were examined by CV (gold standard) and MRA and 17 by CDS. These studies were compared for DVT diagnosis in the pelvis and inferior vena cava and analysis of thrombotic spread. MRA was positive in 25 patients whose DVT was diagnosed by CV (100% sensitivity). MRA sensitivity and negative predictive value were 100%, specificity 98.5% and positive predictive value 97.5% for the diagnosis of thrombosis at each anatomic level. There were discrepancies between MRA and CV (2 false-positive results for 2 venous segments) and between CDS and CV (2 false-positive and 3 false-negative results). CV was uninterpretable for 8.8% of segments and CDS was often technically limited to the pelvic level, whereas all venous segments explored were analysable in MRA. MRA gave excellent results for positive diagnosis and DVT spread. MRA is a potentially valuable technique for assessing iliofemorocaval venous thrombosis.

Feasibility of radioimmunoguided surgery of colorectal carcinoma using indium 111 CEA specific antibody and simulation with a phantom using 2 steps targetting with bispecific antibody.

The study was undertaken to define the potential use of radiolabelled (Indium 111 or Technetium 99 m) carcinoembryonic antigen specific antibody (CEA f(ab')2) for the radioimmunodetection of colorectal cancer using an intraoperative hand-held gamma probe. A clinical study performed with ten patients showed that tumor with good uptake of CEA specific antibody could be detected with sufficient contrast only in two patients. Results of a biodistribution study performed with tumor fragment and normal tissue countings in a gamma counter showed high tumor uptake in five patients. There was no correlation between tumor uptake and the count rates measured intraoperatively. To increase the signal/background of the gamma probe, a simulation study with a peritoneal cavity phantom was performed. We determined the efficiency of a two steps targetting method compared to the direct method. We simulated different tumor sizes with plexiglas balls (0.5, 1, 2, 5 ml) and tested two scintillators (NaI, BgO). Experiments were performed with 111 In and 99 m Tc. The two steps targetting method was better than direct method. The results of simulation with direct method radiolabelled with 111 in confirmed our clinical study: no efficiency of a gamma probe for the surgeon to detect a tumor. However the two steps targetting method (indirect labelling method) was very encouraging to detect tumors (size 1 and 2 ml) and definitively convincing with 99 m Tc.

Radioimmunodetection of medullary thyroid cancer using a bispecific anti-CEA/anti-indium-DTPA antibody and an indium-111-labeled DTPA dimer.

Two-step radioimmunotargeting using a bispecific anti-CEA/anti-in-DTPA monoclonal antibody and an 111In-labeled DTPA dimer (diDTPA-TL) was evaluated nine times in eight patients with medullary thyroid cancer (MTC). Immunoscintigraphy was performed 5 and 24 hr after injection of 111In-diDTPA-TL. For five patients, radioimmunoguided surgery (RIGS) was performed using a hand-held gamma probe (sodium iodine), and a biodistribution study was performed 48 hr (four times) and 24 hr (one time) after injection of 111In-diDTPA-TL. Mean tumor uptake (%ID/kg in tumor) was 39 (range 2.75-139). In these five patients, immunoscintigraphy visualized all known tumors and detected unknown foci (US and CT were negative) in the neck (once) and neck and liver (once). Immunoscintigraphy, performed four times in search of a recurrence, detected unknown localizations in the mediastinum and neck (twice) and was negative twice. There were no false-positives. In three of five patients who had surgery, RIGS localized tumor foci not detected by the surgeon. RIGS failed to detect two small lesions (10 x 10 mm) corresponding to sites of fibrosis and microscopic cancer infiltration. Bispecific anti-CEA/anti-In-DTPA mediated targeting of 111In-diDTPA-TL provided elevated tumor uptake and tumor-to-normal tissue ratios. Radioimmunodetection of small MTC lesions is thus possible even when morphological imaging techniques prove negative.

Biodistribution of anti-CEA F(ab')2 fragments conjugated with chelating polymers: influence of conjugate electron charge on tumor uptake and blood clearance.

F(ab')2 fragments of anti-carcinoembryonic antigen (CEA) monoclonal antibody (mAb) were modified with three chain-terminal polylysine-based chelating polymers so as to carry different electron charges. Immunoreactive conjugates labeled with 111In up to a specific radioactivity of 120-140 microCi/micrograms were injected into nude mice bearing human colorectal carcinoma, and the biodistribution patterns were compared with each other and with that of an anti-CEA F(ab')2-DTPA control. Immunoconjugate modified with positively-charged polymer produced the highest tumor uptake [up to 20% injected dose per gram (ID/g)], with very significant non-specific radioactivity in normal organs (particularly kidneys). When modified with a polymer carrying only a slight negative charge, the immunoconjugate also produced fairly high tumor uptake (up to 18% ID/g), with much lower non-specific radioactivity in normal organs. Highly negatively-charged conjugate produced the lowest tumor uptake (up to 8% ID/g), whereas blood and whole-body clearances were the fastest but slower than those of conventionally labeled F(ab')2 mAb. The possible mechanisms for the effects described are discussed.

Site-specific conjugation of chain-terminal chelating polymers to Fab' fragments of anti-CEA mAb: effect of linkage type and polymer size on conjugate biodistribution in nude mice bearing human colorectal carcinoma.

Polylysine-based chelating polymers were used for site-specific modification of anti-CEA mAb Fab' fragments via their SH group distal to the antigen-binding site of the antibody molecule. Conjugation was performed using chain-terminal (pyridyldithio)propionate or 4-(p-maleimidophenyl)butyrate moieties to form reducible (S-S) or stable (S-C) bonds between a polymer and Fab' molecule, respectively. One S-S conjugate (S-S9) and two different S-C conjugates (S-C3 and S-C9) were prepared using 3- and 9-kDa molecular weight polymers. No significant loss of immunoreactivity was observed in solid-phase immunoassay, 90-95% of 111In-labeled conjugates being bound to CEA-coated Sepharose beads. After labeling with 111In, the conjugates had a specific radioactivity of 90-120 microCi/micrograms. Injected in nude mice bearing LS 174T carcinoma, the conjugates produced different biodistribution patterns. S-S9 was practically unable to accumulate in tumor and produced very rapid blood clearance of radioactivity and high uptake of radioactivity in liver, spleen, and especially kidneys (225% ID/g 24 h postinjection). S-C3 and S-C9 produced practically the same blood clearances (much slower than that of S-S9) and significant tumor uptake (9-10% ID/g at 24 h). S-C3 gave significantly lower radioactivity in spleen, skin, and bones, and cleared more rapidly from liver and kidneys. Renal uptake for S-C3 and S-C9 was rather high (45% ID/g at 24 h), but much lower than for S-S9.

Feasibility study of radioimmunoguided surgery of colorectal carcinomas using indium-111 CEA-specific monoclonal antibody.

The study was undertaken to define the potential use of indium 111 carcinoembryonic antigen-specific antibody labelled [CEA F(ab')2] for the radioimmuno-detection of colorectal carcinoma using an intraoperative hand-held gamma probe. The use of a linear radioactive source allowed optimization of physical characteristics. The best results regarding sensitivity and resolution were obtained using a 5-mm thick tungsten alloy collimator. A simulation study with a liver phantom (22 MBq or 0.6 mCi) was performed to determine the effect of side scatter as opposed to direct background and showed that it is possible to detect small radioactive targets (3.7 KBq or 0.1 mu Ci) 4 cm from the phantom. A clinical study performed with ten patients showed that tumours with good uptake of CEA-specific antibody could be detected with sufficient contrast in two patients when the probe was used. Results of a biodistribution study performed after tumour fragment or normal tissue countings in a well counter showed high tumour uptake (above 8 x 10(-3) injected dose/g) and tumour-to-normal tissue ratios (between 2.5 and 20) in five patients. Results with the probe showed markedly lower ratios. There was no correlation between absolute tumour uptake and the count rates of tumour measured intraoperatively. This can be attributed to the degradation of depth resolution resulting from the high energy photopeak of gamma-emitting 111In.

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.

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.

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.

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.

Selective modification of NMR relaxation time in human colorectal carcinoma by using gadolinium-diethylenetriaminepentaacetic acid conjugated with monoclonal antibody 19-9.

Monoclonal antibody 19-9 (mAb 19-9) against human colon adenocarcinoma was conjugated with gadolinium X diethylenetriaminepentaacetic acid (Gd X DTPA) and used as a contrast agent in nuclear magnetic resonance (NMR) in an effort to improve tumor target selectivity in nude mice. The data indicate that Gd X DTPA-mAb 19-9 in solution decreased the T1 relaxation of water protons at 90 MHz in direct proportion to the gadolinium concentration, and this effect was greater than in Gd X DTPA solutions. T1 relaxation time at 90 MHz, measured in tumors removed from nude mice 24 hr after injection of Gd X DTPA-mAb 19-9 (Gd, 20 mumol/kg; 16 DTPA molecules per mAb molecule), was significantly decreased (by 15%) as compared with the control group. Similar results were obtained in tumors from mice injected with Gd X DTPA-mAb 19-9 solutions in which Gd was used at 2, 6, or 10 mumol/kg (16 DTPA molecules per mAb molecule). These doses are lower than those commonly used for Gd X DTPA (10-100 mumol/kg) as contrast agent. Tumor localization by the Gd X DTPA-mAb 19-9 complex containing radioactive Gd (0.3 microCi/microgram of 153Gd) to confirm scintigraphy revealed significant concentrations of the complex (5% of the injected dose per gram of tissue) in the tumor. Scan images recorded in planar scintigraphy at day 5 showed good visualization of tumors.

Immunotherapy of gastrointestinal cancer with monoclonal antibodies.

Twenty patients with widespread metastatic colorectal carcinoma were infused with 500 mg of the cytotoxic IgG2a monoclonal antibody 17-1A preincubated with autologous peripheral blood leukocytes. Ten patients showed no benefit from such therapy and ten died, with a mean survival time of 7.6 +/- 4.5 months after treatment and a median survival of 6 months. In ten additional patients, the course of disease was modified by antibody therapy; disease in five of these patients stabilized, while tumor size in the other five patients decreased after therapy. Median actual survival in this group of ten patients is presently 24 months; four of these patients died of disease progression within a mean of 15 +/- 5 months. Duration of response was 10.5 +/- 6.7 months after antibody treatment. Treatment tolerance for these 20 patients was excellent in all but one patient, who experienced an anaphylactic reaction during a second infusion with 17-1A.