Richard S. Benua

Perfusion of colorectal hepatic metastases. Relative distribution of flow from the hepatic artery and portal vein

The importance of portal circulation in the delivery of drugs and nutrients to colorectal hepatic metastases is controversial. Using 13N (nitrogen 13) amino acids and ammonia with dynamic gamma camera imaging, we demonstrate, for the first time in human beings, a quantitative advantage of hepatic artery compared with portal vein infusion. Eleven patients were studied by hepatic artery injection, five patients were studied by portal vein injection, and two patients had injections through both routes. Data collected from the liver for 10 minutes after rapid bolus injection of 13N L‐glutamate, L‐glutamine, or ammonia were compared with 99mTc (technetium) macroaggregated albumin (MAA) images produced after injection through the hepatic artery or portal vein at the same session. Tumor regions defined from 99mTc sulfur colloid scans were compared with nearby liver areas of similar thickness. For the 13N compounds, the area‐normalized count rate at first pass maximum (Qmax) and the tissue extraction efficiency were computed. The tumor/liver Qmax ratios for MAA and 13N compounds were highly correlated. Both tumor and liver extracted more than 70% of the nitrogenous compounds. The tumor/liver Qmax ratios reflect the relative delivery of injected tracer per unit volume of tissue. After hepatic artery injection the Qmax ratio was 1.03 ± 0.33 (mean ± SD), significantly exceeding the Qmax ratio of 0.50 ± 0.34 after portal vein injection (P < 0.003). Therefore, (1) more than twice as much of a nutrient substrate is delivered per volume of tumor relative to liver by the hepatic artery as by the portal vein; (2) the high extraction efficiency demonstrates that the hepatic artery flow is nutritive; and (3) the delivery of substance in solution (such as nutrients or drugs) to tumor and liver tissue correlates with the distribution of colloids such as macroaggregated albumin after hepatic arterial and portal venous injection.

The value of diagnostic aids in detecting pancreas cancer.

By contract with the National Cancer Institute, the accuracy of diagnostic techniques was assessed in 184 patients suspected of having pancreas cancer. Of 138 patients who were operated upon, 89 were found to have pancreas duct cancer, 30 had cancer of a different site of origin in the head of the pancreas region and in 19 there was no evidence of cancer at operation. All of the 46 patients who were not operated upon, 13 proven to have cancer and 33 patients discharged as free of cancer, were followed in our clinic. The majority of our patients presented with signs and symptoms of biliary obstruction. Computerized transaxial tomography (CTT) gave a “correct” diagnosis in 31 of 33 patients (94%) with proven cancer, there were 2 patients with a false negative report and a false positive diagnosis occurred in 8 of 20 patients (40%) without cancer. Celiac angiography (CA) gave a correct diagnosis in 78 of 94 patients (83%) with cancer, a false negative in 17%, and a false positive in 32%. 75Sele‐nomethionine pancreas scan correctly diagnosed 27 of 36 patients (75%) with cancer, gave a false negative in 25% and a false positive in 31%. Ultrasonog‐raphy gave a correct diagnosis in 18 of 27 patients with cancer (67%), a false negative in 33% and a false positive in 28%. Endoscopic retrograde cholangio‐pancreatography diagnosed correctly 8 of 11 cases (73%) of cancer, there were false negative diagnoses in 3 cases (27%) and false positives in 3 of 14 patients (21%). Duodenal aspiration techniques gave a very low percentage of correct diagnoses. Chronic pancreatitis most commonly gave rise to a false positive diagnosis. Serum alkaline phosphatase was elevated in 82% of patients, gave 18% false negatives and 33% false positives. Carcinoembryonic antigen (CEA) was elevated (> 2.5 ng/ml) in most of the pancreas cancer patients but also in patients with other cancers and with non‐cancerous diseases. In our hands, CTT, CA, alkaline phosphatase, 75Se‐methionine and ultrasonography, in descending order, have given the highest percentage of correct diagnoses but false positive and false negative diagnoses prevented any single test from being conclusive.

Predicting tumor response in patients with colorectal hepatic metastases.

Until now, there has been no reliable means of predicting tumor response to chemotherapy in patients with metastatic colorectal cancer. Using arterial nuclide flow scans as a determinant of tumor response, the degree of tumor perfusion was evaluated in a blinded prospective study. Seventy-three patients with colorectal hepatic metastases received continuous hepatic arterial (N = 52) or systemic intravenous (N = 21) chemotherapy using an implantable pump. All patients had pretreatment hepatic arteriography and arterial flow scans using 99mTc macroaggregated albumin (99mTc-MAA). An arteriogram was characterized as positive if it showed tumor hypervascularity; the 99mTc-MAA flow scan was considered positive if it showed increased tumor uptake relative to the liver. Of 47 patients with an evaluable 99mTc-MAA flow scan who were treated with arterial infusion, 31 had a positive scan; in this group 16 responded to chemotherapy. The 99mTc-MAA scan was negative in 16 patients, of whom one responded to chemotherapy (p less than 0.006). The 99mTc-MAA scan had the greatest predictive value in previously untreated patients (sensitivity = 91%; specificity = 77%). The arteriogram was positive in 25 of 46 evaluable patients, but this finding had little predictive value for tumor response (sensitivity = 56%; specificity = 46%). Of 21 patients receiving systemic intravenous infusion, the scan was positive in nine patients, of whom seven responded to chemotherapy. The 99mTc-MAA scan was negative in 12 patients, of whom one responded to chemotherapy (sensitivity = 88%; specificity = 85%). When 99mTc-MAA-positive and -negative groups were compared, there were no differences in mean patient age, per cent liver involvement, tumor size, or plasma liver function tests. Hepatic tumor perfusion as determined by MAA arterial flow scan is a reliable predictor of tumor response in patients with metastases from large bowel cancer. The test provides a valuable criterion for selecting individuals for treatment of metastases from large bowel cancer by infusion chemotherapy.

Intratumoral consumption of indium-111 labeled platelets in a patient with hemangiomatosis and intravascular coagulation (Kasabach-Merritt syndrome)

Previous studies regarding sites of platelet destruction in patients with the Kasabach‐Merritt syndrome are conflicting. The authors recently studied an adult patient with multiple large hemangiomata, thrombocytopenia, and intravascular coagulation by external imaging following the injection of autologous Indium‐111 labeled platelets. Sequential images showed prompt accumulation of platelet‐associated radioactivity in areas within the right hemithorax which corresponded to certain tumors noted on the chest roentgenogram. Despite the presence of multiple other lesions in bone and soft tissues, platelet radioactivity was otherwise normally confined to liver and spleen. Using data obtained from serial images, it was shown that radioactivity within the thoracic masses actually increased over time. These data indicate that platelet consumption occurred as an active process and that localization was not a result of tumor vascularity. It is concluded that platelets are locally consumed within certain hemangiomata. However, within the same individual, there may exist considerable heterogeneity among these tumors with respect to platelet‐trapping ability. In similar patients with multiple tumors, indium‐platelet scanning might be used to direct local therapy to particular lesions in an effort to correct the thrombocytopenia. Cancer 52:256‐2260, 1983.

Abnormal Gallium Scintigraphy in Pneumocystis Carinii Pneumonia with a Normal Chest Radiograph

The authors describe a patient with malignant lymphoma in whom the use of a 67Ga citrate lung scan assisted in the diagnosis of P. carinii pneumonia. In immunodeficient patients presenting with unexplained fever, abnormal pulmonary function tests, a normal chest radiograph, and few chest symptoms, the 67Ga citrate scan may lead to the early detection and successful treatment of this potentially lethal infection.

Tumor imaging with carbon-11 labeled alpha-aminoisobutyric acid (AIB) in a patient with advanced malignant melanoma

A 29 year-old-man presenting with advanced metastatic malignant melanoma was successfully imaged using carbon-11 (11C) labeled alpha-aminoisobutyric acid (AIB), a synthetic, non-metabolized amino acid transported into viable cells by the A-type, or alanine-preferring, amino acid transport system. Tumor located in the hilum of the lung was well visualized with 11C-AIB prior to chemotherapy. A gallium image with liver subtraction using 99mTc-sulfur colloid demonstrated regions of increased activity in liver which correlated with regions of increased activity on the 11C-AIB liver image.

Semiquantitative gallium scintigraphy in patients with osteogenic sarcoma

Sequential gallium scans were performed in 37 patients with newly diagnosed osteogenic sarcoma. High gallium uptake was found more often in males in the 10 to 19 age group and in femoral lesions. High uptake was also seen in patients who had predominantly osteoblastic or mixed changes on radiographs and in those who had a soft tissue mass. Following chemotherapy, significant decrease of tumor to nontumor ratio occurred in the patients who responded to treatment as shown by a Grade III or IV response on histologic examinations at the time of en bloc resection. It is concluded that semiquantitative gallium scintigraphy is useful in monitoring therapeutic response in patients with osteogenic sarcoma.

Quotient imaging with N‐ 13 L‐glutamate in osteogenic sarcoma: Correlation with tumor viability

An investigation was performed to correlate the regional uptake of N‐13 L‐glutamate with histologic changes in tumor tissue in patients undergoing adjuvant chemotherapy for osteogenic sarcoma. A parametric image was produced by calculating the ratio of N‐13 uptake in the tumor in a pixel‐by‐pixel fashion, using the presurgical scan as the numerator and the pretherapy scan as the denominator. The change in N‐13 uptake in 2 × 2‐cm regions of the tumor was compared with residual cell viability as determined by microscopic examination of multiple thin sections obtained from the surgical specimens. Regions that showed decreases in N‐13 uptake of more than 30% were frequently associated with areas of highly necrotic tumor, and regions that showed increasing uptake were associated with high residual cell viability and incomplete response to chemotherapy.

Imaging studies of patients with malignant fibrous histiocytoma using C-11-alpha-aminoisobutyric acid (AIB).

Alpha-aminoisobutyric acid (AIB), a synthetic, nonmetabolized amino acid which is rapidly transported into viable cells by the A-type or alanine-preferring amino acid transport system, has been labeled with the shortlived, positron-emitting radionuclide carbon-11. Carbon-11 labeled AIB is currently being evaluated as a tumor imaging agent for in vivo amino acid transport studies in patients with cancer. In this study, C-11 AIB was used to image two patients with malignant fibrous histiocytoma (MFH), a pleomorphic sarcoma. Following intravenous administration of C-11 AIB, tumors in the distal femur of one patient and in the anterior chest wall of another patient were well visualized using high energy gamma scintigraphy. Since therapy may alter the accumulation of amino acids in tumor tissue, studies using C-11 AIB in patients with MFH before and after chemotherapy are in progress.

Correlation between iodine-131 MIBG imaging and biological markers in advanced neuroblastoma

I-131 metaiodobenzylguanidine (MIBG) imaging was performed in 38 patients with advanced neuroblastoma. Abnormal images were found in patients with elevations of urinary vanillylmandelic acid and dopamine and high serum neuron-specific enolase levels. Normal or minimal elevation of markers was seen in patients with negative images. In follow-up studies after chemotherapy, the disappearance of abnormal uptake was noted in those patients with normal marker values. A persistently abnormal uptake occurred in patients with high marker values. Conversion from a normal image to an abnormal image also occurred in patients whose markers became elevated. I-131 MIBG imaging is sensitive in detecting active foci of a neuroblastoma and is useful in monitoring chemotherapy in these patients.